Zebrafish hox genes: expression in the hindbrain region of wild-type and mutants of the segmentation gene, valentino

Development ◽  
1998 ◽  
Vol 125 (3) ◽  
pp. 393-406 ◽  
Author(s):  
V.E. Prince ◽  
C.B. Moens ◽  
C.B. Kimmel ◽  
R.K. Ho
Keyword(s):  
Gene Expression ◽  
Gene Product ◽  
Hox Genes ◽  
Developmental Stages ◽  
Expression Profiles ◽  
Critical Role ◽  
Loss Of Function ◽  
Hox Gene ◽  
Segmentation Gene ◽  
Functional Changes

The developing hindbrain is organized into a series of segments termed rhombomeres which represent lineage restricted compartments correlating with domains of gene expression and neuronal differentiation. In this study, we investigate the processes of hindbrain segmentation and the acquisition of segmental identity by analyzing the expression of zebrafish hox genes in the hindbrains of normal fish and fish with a loss-of-function mutation in the segmentation gene valentino (val, the homologue of mouse kreisler; Moens, C. B., Cordes, S. P. Giorgianni, M. W., Barsh, G. S. and Kimmel, C. B. (1998). Development 125, 381–391). We find that zebrafish hox genes generally have similar expression profiles to their murine and avian counterparts, although there are several differences in timing and spatial extent of expression which may underlie some of the functional changes that have occurred along the separate evolutionary lineages of teleosts and tetrapods. Our analysis of hox gene expression in val- embryos confirms that the val gene product is important for subdivision of the presumptive rhombomere 5 and 6 territory into definitive rhombomeres, suggests that the val gene product plays a critical role in regulating hox gene transcription, and indicates that some neural crest cells are inappropriately specified in val- embryos. Our analysis of gene expression at several developmental stages has allowed us to infer differences between primary and secondary defects in the val mutant: we find that extended domains of expression for some hox genes are secondary, late phenomena potentially resulting from inappropriate cell mixing or lack of normal inter-rhombomeric interactions in the caudal hindbrain.

The CALM/AF10 Fusion: Molecular Analysis of the Fusion Transcripts in 13 Cases of AML and ALL; Gene Expression Profiling Reveals HOX Gene Deregulation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2895-2895 ◽  
Author(s):  
Alexandre Krause ◽  
Alexander Kohlmann ◽  
Torsten Haferlach ◽  
Claudia Schoch ◽  
Susanne Schnittger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fusion Protein ◽  
Hox Genes ◽  
Lymphoblastic Leukemia ◽  
Critical Role ◽  
Gene Clusters ◽  
Dominant Negative ◽  
Nucleotide Position ◽  
Gamma Delta ◽  
Hox Gene

Abstract The t(10;11)(p13;q14) is a recurring translocation associated with the CALM/AF10 fusion gene which is found in undifferentiated leukemia, acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma with poor prognosis. The CALM/AF10 fusion protein was reported to be the most common fusion protein in T-ALL with TCR gamma delta rearrangement. We have analyzed samples from 9 patients with different types of leukemia: case 1 (AML M2), case 2 (AML M0), case 3 (Pre T-ALL), case 4 (Acute Undifferentiated Leukemia), case 5 (PreT-ALL), case 6 and 7 (ProT-ALL), case 8 (T-ALL), case 9 (AML), with a t(10;11) translocation suggesting a CALM/AF10-rearrangement. The samples were analyzed for the presence of the CALM/AF10 and AF10/CALM mRNA by RT-PCR and sequence analysis. All these patients were found positive for the CALM/AF10 fusion. In addition, we analyzed a series of twenty-nine patients with T-ALL with gamma delta rearrangement. Among these patients, four were positive for CALM/AF10 transcripts, indicating a high incidence of CALM/AF10 fusions in this group of leukemia. We found three different breakpoints in CALM at nucleotide 1926, 2091 and a new exon, with 106 bases inserted after nt 2064 of CALM in patient 4. In AF10 four breakpoints were identified: at nucleotide position 424, 589, 883 and 979. In seven patients it was also possible to amplify the reciprocal AF10/CALM fusion transcript (case 1, 3, 4, 8, 9, 10 and 11). There was no correlation between disease phenotype and breakpoint location. The patients were 5 to 46 years old (median 25). Ten CALM/AF10 positive patients were further analyzed using oligonucleotide microarrays representing 33,000 different genes (U133 set, Affymetrix). Analysis of microarray gene expression signatures of these patients revealed high expression levels of the homeobox gene MEIS1 and the HOXA cluster genes HOXA1, HOXA4, HOXA5, HOXA7, HOXA9, and HOXA10. The overexpression of HOX genes seen in these CALM/AF10 positive leukemias is reminiscent of the pattern seen in leukemias with rearrangements of the MLL gene, and complex aberrant karyotypes suggesting a common effector pathway (i.e. HOX gene deregulation) for these diverse leukemias. It is known that alhambra, the Drosophila homologue of AF10 can act on polycomb group responsive elements, which play a critical role in the regulation of the HOX gene clusters. It is thus conceivable that the CALM/AF10 fusion proteins acts in a dominant negative fashion on wild type AF10 function relieving the repression that is presumably normally exerted by AF10 on the expression of HOX genes.

Regulation of Hox Genes by Polycomb Group Protein EZH2 Plays a Critical Role in Diffuse Large B-Cell Lymphoma Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1562-1562
Author(s):  
Irina Velichutina ◽  
Ari Melnick
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
Target Genes ◽  
Hox Genes ◽  
Critical Role ◽  
Polycomb Group ◽  
Lymphoma Cells ◽  
Self Renewal ◽  
Hox Gene ◽  
Large B Cell

Abstract Coordinated regulation of Hox gene expression during hematopoiesis is epigenetically controlled via chromatin modification by Polycomb group (PcG) and Trithorax (MLL) protein complexes. Whereas the oncogenic potential of certain HOX genes in leukemia has already been defined, little is known about their role in Diffuse Large B-cell Lymphomas (DLBCL). The primary focus of our studies is to determine the contribution of PcG-mediated repression of HOX and other genes to DLBCL pathogenesis. The PcG protein, Ezh2, is vital for maintaining both pluripotency of stem cells and identity of differentiated cells. Ezh2 tri-methylates lysine K27 of histone 3 (H3K27me3), a histone modification associated with gene silencing. Importantly, Ezh2 is frequently overexpressed in DLBCLs suggesting a role for EZH2 in lymphomagenesis. In support to this notion we discovered that Ezh2 is essential for DLBCL cell survival. By depleting Ezh2 level using RNAi, we found that loss of Ezh2 triggers cell cycle arrest and death of DLBCL cells. This finding prompted us to initiate functional studies aimed at uncovering Ezh2 target genes that mediate the observed cellular response in DLBCL cells. We first focused on a potential role of Ezh2 in regulation of HOX genes. We compared and contrasted Ezh2 targets in both normal Germinal Center (GC) B-cells and GC-derived DLBCLs to determine the normal and pathologic function of EZH2. We employed a tiling ChIP-chip approach covering the four human HOX clusters and mapped Ezh2 and H3K27m3 within HOX gene clusters. We further verified gene expression status of a subset of Hox genes by QPCR. These data indicated that Ezh2 and its cognate H3K27m3 mark are present at promoters of HoxC genes in both mature GC B-cells and GC-derived lymphoma cells, thereby driving the HoxC locus silent, suggesting that both rapidly dividing GC cells and GC-derived lymphoma cells require epigenetic silencing of this locus in order to maintain their phenotype. Both Ezh2 and the corresponding H3K27m3 transcription repression mark are absent within the promoter region of HoxA9 gene. HoxA9 promotes stem cell self-renewal and it is aberrantly activated in AML cells. This observation is especially striking as the HoxA9 is embedded into the Ezh2-sealed region in DLBCL cells, suggesting an Ezh2-independent mode of regulation. We are in the process of testing functional significance of this finding for lymphoma pathogenesis. we found that HoxB genes that are differentially expressed in progenitor vs. lineage committed cells are silent in DLBCL cells according to H3K27m3/Ezh2 pattern and gene expression analysis. Intriguingly, the early progenitor specific gene, HoxB3, is uniquely not bound by EZH2 nor H3K27 methylated and was highly expressed in lymphoma cells. This finding underscores a potential functional significance of re-expression of genes that control cell self-renewal in malignances that derive from mature B cells. We also examined transcriptional programming by EZH2 at the genomic level by ChIP-on-chip using NimbleGen 24,000 promoter arrays. EZH2 was bound to ∼1700 promoters in DLBCL cells and a similar number of genes displayed H3K27 methylation. Gain and loss of function studies are underway to identify the contribution of the most likely EZH2 direct targets genes to the DLBCL survival including both HOX genes and other genomic direct target genes. Taken together, our data suggest a critical role for EZH2 mediated epigenetic silencing of HOX and other genes in DLBCL - and implicate aberrant HOX gene expression in DLBCL pathogenesis.

scholarly journals Staggered Hox expression is more widespread among molluscs than previously appreciated

2018 ◽  
Vol 285 (1888) ◽  
pp. 20181513 ◽  
Author(s):  
Tim Wollesen ◽  
Sonia Victoria Rodríguez Monje ◽  
André Luiz de Oliveira ◽  
Andreas Wanninger
Keyword(s):  
Gene Expression ◽  
Morphological Traits ◽  
Hox Genes ◽  
Developmental Stages ◽  
Early Stage ◽  
Genomic Data ◽  
Published Data ◽  
Hox Gene ◽  
The Central Nervous System ◽  
Anterior Posterior

Hox genes are expressed along the anterior–posterior body axis in a colinear fashion in the majority of bilaterians. Contrary to polyplacophorans, a group of aculiferan molluscs with conserved ancestral molluscan features, gastropods and cephalopods deviate from this pattern by expressing Hox genes in distinct morphological structures and not in a staggered fashion. Among conchiferans, scaphopods exhibit many similarities with gastropods, cephalopods and bivalves, however, the molecular developmental underpinnings of these similar traits remain unknown. We investigated Hox gene expression in developmental stages of the scaphopod Antalis entalis to elucidate whether these genes are involved in patterning morphological traits shared by their kin conchiferans. Scaphopod Hox genes are predominantly expressed in the foot and mantle but also in the central nervous system. Surprisingly, the scaphopod mid-stage trochophore exhibits a near-to staggered expression of all nine Hox genes identified. Temporal colinearity was not found and early-stage and late-stage trochophores, as well as postmetamorphic individuals, do not show any apparent traces of staggered expression. In these stages, Hox genes are expressed in distinct morphological structures such as the cerebral and pedal ganglia and in the shell field of early-stage trochophores. Interestingly, a re-evaluation of previously published data on early-stage cephalopod embryos and of the gastropod pre-torsional veliger shows that these developmental stages exhibit traces of staggered Hox expression. Considering our results and all gene expression and genomic data available for molluscs as well as other bilaterians, we suggest a last common molluscan ancestor with colinear Hox expression in predominantly ectodermal tissues along the anterior–posterior axis. Subsequently, certain Hox genes have been co-opted into the patterning process of distinct structures (apical organ or prototroch) in conchiferans.

scholarly journals Hox genes and morphological identity: axial versus lateral patterning in the vertebrate mesoderm

Development ◽  
2000 ◽  
Vol 127 (19) ◽  
pp. 4265-4275 ◽  
Author(s):  
J.L. Nowicki ◽  
A.C. Burke
Keyword(s):  
Gene Expression ◽  
Hox Genes ◽  
Expression Profiles ◽  
The Body ◽  
Lateral Plate ◽  
Global Pattern ◽  
Hox Gene ◽  
Embryonic Origin ◽  
Morphological Identity ◽  
Derivatives Of

The successful organization of the vertebrate body requires that local information in the embryo be translated into a functional, global pattern. Somite cells form the bulk of the musculoskeletal system. Heterotopic transplants of segmental plate along the axis from quail to chick were performed to test the correlation between autonomous morphological patterning and Hox gene expression in somite subpopulations. The data presented strengthen the correlation of Hox gene expression with axial specification and focus on the significance of Hox genes in specific derivatives of the somites. We have defined two anatomical compartments of the body based on the embryonic origin of the cells making up contributing structures: the dorsal compartment, formed from purely somitic cell populations; and the ventral compartment comprising cells from somites and lateral plate. The boundary between these anatomical compartments is termed the somitic frontier. Somitic tissue transplanted between axial levels retains both original Hox expression and morphological identity in the dorsal compartment. In contrast, migrating lateral somitic cells crossing the somitic frontier do not maintain donor Hox expression but apparently adopt the Hox expression of the lateral plate and participate in the morphology appropriate to the host level. Dorsal and ventral compartments, as defined here, have relevance for experimental manipulations that influence somite cell behavior. The correlation of Hox expression profiles and patterning behavior of cells in these two compartments supports the hypothesis of independent Hox codes in paraxial and lateral plate mesoderm.

Artificial Neural Network Analysis of HOX Gene Expression Profiles Predicts Prognostic Subgroups in Acute Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2318-2318
Author(s):  
Damian P.J. Finnegan ◽  
Michael F. Quinn ◽  
Mervyn Humphreys ◽  
Terence R.J. Lappin ◽  
Mary Frances McMullin ◽  
...  
Keyword(s):  
Neural Network ◽  
Gene Expression ◽  
Artificial Neural Network ◽  
Hox Genes ◽  
Expression Profiles ◽  
Hox Gene ◽  
Prognostic Groups ◽  
Prognostic Group ◽  
Prognosis Group ◽  
Artificial Neural

Abstract The acute myeloid leukemias (AMLs) are a heterogeneous group of hematological malignancies with diverse clinical outcomes. Pre-treatment karyotype analysis identifies biologically distinct subgroups and is currently used as a predictor of response to induction chemotherapy and risk of relapse. Cases may be stratified into one of three prognostic groups as follows: relatively favorable prognosis [t(8;21), t(15;17) and inv(16)]; adverse prognosis [−5/del(5q), −7, abnormalities of chromosome 3q and complex karyotype]; and intermediate prognosis [remainder including normal karyotype]. HOX genes encode master transcription factors which regulate key developmental processes including differentiation, proliferation and apoptosis. Humans have 39 HOX genes and multiple lines of evidence implicate their deregulated expression in the pathogenesis of AML. Drabkin et al. (Leukemia2002; 16: 186–95) have reported that AMLs with a relatively favorable prognostic karyotype are associated with low levels of HOX gene expression whereas AMLs with an adverse prognostic karyotype have higher levels of expression. To further characterize HOX gene expression in cytogenetic prognostic groups we determined the expression profiles of 26 HOX genes by real-time quantitative PCR (Q-PCR) in diagnostic samples, representative of the three prognostic groups, from 26 patients with de novo AML. Profiles were then analyzed using Artificial Neural Network based computational approaches to identify a subset of HOX genes which could discriminate between prognostic groups in a predictive fashion. Predictive models were developed for each prognostic group. Predictive classification performance for prognostic groups based on blind data of 88%, 92%, and 97% (with equal sensitivity and specificity) were achieved for the three prognostic groups. The models were interrogated to determine the nature of the relationship between the key HOX genes identified and prognostic group. The relatively favorable prognosis group was primarily defined by downregulation of HOXA5 and upregulation of HOXC4. The intermediate prognosis group was characterized by upregulation of HOXB3 and downregulation of HOXD10 and the adverse prognosis group by downregulation of both HOXC5 and HOXD3. Although the sample size is small, the results show that Artificial Neural Network based computational approaches are capable of further characterizing HOX gene expression within AML prognostic groups as determined by presenting karyotype and that measuring the expression levels of a small number of HOX genes at diagnosis can provide useful clinical information in cases where karyotype analysis has been unsuccessful.

scholarly journals Genome-Wide Identification of Soybean ABC Transporters Relate to Aluminum Toxicity

2021 ◽  
Vol 22 (12) ◽  
pp. 6556
Author(s):  
Junjun Huang ◽  
Xiaoyu Li ◽  
Xin Chen ◽  
Yaru Guo ◽  
Weihong Liang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Abc Transporters ◽  
Developmental Stages ◽  
Aluminum Toxicity ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Purifying Selection ◽  
Biotic Stresses ◽  
Genome Wide ◽  
New Germplasm

ATP-binding cassette (ABC) transporter proteins are a gene super-family in plants and play vital roles in growth, development, and response to abiotic and biotic stresses. The ABC transporters have been identified in crop plants such as rice and buckwheat, but little is known about them in soybean. Soybean is an important oil crop and is one of the five major crops in the world. In this study, 255 ABC genes that putatively encode ABC transporters were identified from soybean through bioinformatics and then categorized into eight subfamilies, including 7 ABCAs, 52 ABCBs, 48 ABCCs, 5 ABCDs, 1 ABCEs, 10 ABCFs, 111 ABCGs, and 21 ABCIs. Their phylogenetic relationships, gene structure, and gene expression profiles were characterized. Segmental duplication was the main reason for the expansion of the GmABC genes. Ka/Ks analysis suggested that intense purifying selection was accompanied by the evolution of GmABC genes. The genome-wide collinearity of soybean with other species showed that GmABCs were relatively conserved and that collinear ABCs between species may have originated from the same ancestor. Gene expression analysis of GmABCs revealed the distinct expression pattern in different tissues and diverse developmental stages. The candidate genes GmABCB23, GmABCB25, GmABCB48, GmABCB52, GmABCI1, GmABCI5, and GmABCI13 were responsive to Al toxicity. This work on the GmABC gene family provides useful information for future studies on ABC transporters in soybean and potential targets for the cultivation of new germplasm resources of aluminum-tolerant soybean.

Analysis of Hox gene expression in the chick limb bud

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1449-1466 ◽  
Author(s):  
C.E. Nelson ◽  
B.A. Morgan ◽  
A.C. Burke ◽  
E. Laufer ◽  
E. DiMambro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Sonic Hedgehog ◽  
Hind Limb ◽  
Hox Genes ◽  
Expression Patterns ◽  
Limb Bud ◽  
Posterior Portion ◽  
Hox Gene ◽  
Hoxd Gene

The vertebrate Hox genes have been shown to be important for patterning the primary and secondary axes of the developing vertebrate embryo. The function of these genes along the primary axis of the embryo has been generally interpreted in the context of positional specification and homeotic transformation of axial structures. The way in which these genes are expressed and function during the development of the secondary axes, particularly the limb, is less clear. In order to provide a reference for understanding the role of the Hox genes in limb patterning, we isolated clones of 23 Hox genes expressed during limb development, characterized their expression patterns and analyzed their regulation by the signalling centers which pattern the limb. The expression patterns of the Abd-B-related Hoxa and Hoxd genes have previously been partially characterized; however, our study reveals that these genes are expressed in patterns more dynamic and complex than generally appreciated, only transiently approximating simple, concentric, nested domains. Detailed analysis of these patterns suggests that the expression of each of the Hoxa and Hoxd genes is regulated in up to three independent phases. Each of these phases appears to be associated with the specification and patterning of one of the proximodistal segments of the limb (upper arm, lower arm and hand). Interestingly, in the last of these phases, the expression of the Hoxd genes violates the general rule of spatial and temporal colinearity of Hox gene expression with gene order along the chromosome. In contrast to the Abd-B-related Hoxa and Hoxd genes, which are expressed in both the fore and hind limbs, different sets of Hoxc genes are expressed in the two limbs. There is a correlation between the relative position of these genes along the chromosome and the axial level of the limb bud in which they are expressed. The more 3′ genes are expressed in the fore limb bud while the 5′ genes are expressed in the hind limb bud; intermediate genes are transcribed in both limbs. However, there is no clear correlation between the relative position of the genes along the chromosome and their expression domains within the limb. With the exception of Hoxc-11, which is transcribed in a posterior portion of the hind limb, Hoxc gene expression is restricted to the anterior/proximal portion of the limb bud. Importantly, comparison of the distributions of Hoxc-6 RNA and protein products reveals posttranscriptional regulation of this gene, suggesting that caution must be exercised in interpreting the functional significance of the RNA distribution of any of the vertebrate Hox genes. To understand the genesis of the complex patterns of Hox gene expression in the limb bud, we examined the propagation of Hox gene expression relative to cell proliferation. We find that shifts in Hox gene expression cannot be attributed to passive expansion due to cell proliferation. Rather, phase-specific Hox gene expression patterns appear to result from a context-dependent response of the limb mesoderm to Sonic hedgehog. Sonic hedgehog (the patterning signal from the Zone of Polarizing Activity) is known to be able to activate Hoxd gene expression in the limb. Although we find that Sonic hedgehog is capable of initiating and polarizing Hoxd gene expression during both of the latter two phases of Hox gene expression, the specific patterns induced are not determined by the signal, but depend upon the temporal context of the mesoderm receiving the signal. Misexpression of Sonic hedgehog also reveals that Hoxb-9, which is normally excluded from the posterior mesenchyme of the leg, is negatively regulated by Sonic hedgehog and that Hoxc-11, which is expressed in the posterior portion of the leg, is not affected by Sonic hedgehog and hence is not required to pattern the skeletal elements of the lower leg.

scholarly journals The Role of Histone Demethylases and DNA Methyltransferases in the Transcription Regulation of HOX Genes in PML-RARa+ AML Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3921-3921
Author(s):  
Katerina Rejlova ◽  
Alena Musilova ◽  
Martina Slamova ◽  
Karel Fiser ◽  
Karolina Skvarova Kramarzova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hox Genes ◽  
Fold Increase ◽  
Dna Methyltransferases ◽  
Histone Mark ◽  
Gene Promoters ◽  
Histone Demethylases ◽  
Atra Treatment ◽  
Hox Gene

Abstract Homeobox genes (HOX) encode transcription factors that are frequently deregulated in leukemias. Our previous results showed that HOX gene expression differs among genetically characterized subtypes of pediatric acute myeloid leukemia (AML). Specifically, PML-RARa positive AML patients have overall lowest HOX gene expression which positively correlates with expression of histone 3 lysine 27 (H3K27) demethylases - JMJD3 and UTX and negatively with the expression of DNA methyltransferases - DNMT3a and DNMT3b. Interestingly, JMJD3 was already shown to be a direct target of PML-RARa protein (Martens, JH et al, 2010, Cancer Cell). From these findings we postulated a hypothesis that reduced levels of HOX genes in PML-RARa positive AML are a consequence of suppressed expression of histone demethylases resulting in increased H3K27 methylation and/or of elevated levels of DNMTs leading to de novoDNA methylation. We studied the role of histone demethylases and DNMTs in the regulation of HOX gene expression and the effect of treatment in PML-RARa positive cell lines (NB4 and ATRA-resistant clones NB4-LR2 and NB4-MR2). We treated NB4 cell line by all-trans retinoic acid (ATRA; 1uM), which was described to release the differentiation block caused by the presence of PML-RARa and to degrade the fusion protein. We observed that expression of particular HOX genes (HOXA1, HOXA3, HOXA4, HOXA5, HOXA7, HOXB4, HOXB6) measured by qPCR was significantly increased after ATRA treatment. While the level of JMJD3 was significantly increased upon ATRA treatment as well, the expression of UTX did not change. Furthermore, we detected significantly reduced expression of DNMT3b gene. To exclude a non-specific effect of ATRA, independent of PML-RARa, we used resistant clones LR2 and MR2 bearing mutations in retinoic acid-binding domain. HOX gene expression together with JMJD3, UTX and DNMT3b expression did not change upon ATRA treatment. These results confirm the PML-RARa-dependent regulation of HOX genes. To test the role of JMJD3 in the HOX gene expression regulation, we cultured NB4 cells with a specific inhibitor of histone demethylases, GSK-J4 (1 uM, 10 uM), in the presence of ATRA. The co-treatment caused significant decrease in the expression of studied HOX genes (HOXA1, HOXA3, HOXA5, HOXA7, HOXA10, HOXB4, HOXB6) in comparison to ATRA alone which supports the role of JMJD3 in the transcription regulation. Further, we performed chromatin immunoprecipitation (ChIP) to investigate if the changes of HOX gene expression upon ATRA and GSK-J4 treatment would correspond with changes of histone code on HOX gene promoter regions. ATRA treatment caused reduction of repressive histone mark (H3K27me3) on particular HOX gene promoters (HOXA1, HOXA3, HOXA5, HOXA7), by contrast, combinational treatment of ATRA and GSK-J4 reversed this effect. Accordingly, we detected that ATRA/GSK-J4 co-treatment reduced active histone mark H3K4me2. Next we were interested if JMJD3 inhibition would interfere with the differentiation effect of ATRA. As shown previously, ATRA treatment alone caused differentiation of NB4 cell line whereas the combination with GSK-J4 did not reduce the effect. Interestingly, in addition to differentiation it led cells to apoptosis. Combination of drugs (ATRA - 1uM, GSK-J4 - 1, 2, 5uM) increased significantly the percentage of dead cells in comparison to ATRA or GSK treatment alone (GSK-J4 alone vs in combination with ATRA, 1uM - 1.8 fold, 2uM - 2.2 fold, 5 uM - 2.3 fold increase). Next we measured apoptosis in resistant clones LR2 and MR2. In both cases the highest concentration used of GSK-J4 (5uM) in combination with ATRA caused significant increase of dead cells as well (LR2 - 2.1 fold, MR2 - 2.0 fold increase). Our results indicate that JMJD3 is responsible for the regulation of HOX gene expression in PML-RARa positive leukemia since changes of HOX gene expression correspond with histone modifications on the regions of HOX gene promoters. We assume that DNA methylation driven by DNMT3b can also participate in this process. Moreover, our findings demonstrate potential therapeutic implications of GSK-J4 inhibitor in combination with ATRA in patients with acute promyelocytic leukemia who are not responsive to ATRA monotherapy. Supported by P304/12/2214 and GAUK 196616 Disclosures No relevant conflicts of interest to declare.

scholarly journals Transcriptomic profiles of non-embryogenic and embryogenic callus cells in a highly regenerative Upland Cotton line (Gossypium hirsutum L.)

2020 ◽  
Author(s):  
Li Wen ◽  
Wei Li ◽  
Stephen Parris ◽  
Matthew West ◽  
John Lawson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Somatic Embryogenesis ◽  
Transcription Factors ◽  
Gossypium Hirsutum ◽  
Embryogenic Callus ◽  
Developmental Stages ◽  
Baby Boom ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Study Gene Expression

Abstract • Background • Genotype independent transformation and whole plant regeneration through somatic embryogenesis relies heavily on the intrinsic ability of a genotype to regenerate. • Results • In this study, gene expression profiles of a highly regenerable Gossypium hirsutum L. cultivar, Jin668, were analyzed at two critical developmental stages during somatic embryogenesis, non-embryogenic callus (NEC) cells and embryogenic callus (EC) cells. The rate of EC formation in Jin668 is 96%. Differential gene expression analysis revealed a total of 5,333 differentially expressed genes (DEG) with 2,534 upregulated and 2,799 downregulated in EC. A total of 144 genes were unique to NEC cells and 174 genes unique to EC. Clustering and enrichment analysis identified genes upregulated in EC that function as transcription factors/DNA binding, phytohormone response, oxidative reduction, and regulators of transcription; while genes categorized in methylation pathways were downregulated. Four key transcription factors were identified based on their sharp upregulation in EC tissue; LEAFY COTYLEDON 1 (LEC1), BABY BOOM (BBM), FUSCA (FUS3) and AGAMOUS-LIKE15 with distinguishable subgenome expression bias. • Conclusions • This comparative analysis of NEC and EC transcriptomes gives new insights into the genetic underpinnings of somatic embryogenesis in cotton.

scholarly journals miRNAome expression profiles in the gonads of adultMelopsittacus undulatus

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4615 ◽  
Author(s):  
Lan Jiang ◽  
Qingqing Wang ◽  
Jue Yu ◽  
Vinita Gowda ◽  
Gabriel Johnson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Early Development ◽  
Expression Profiles ◽  
Critical Role ◽  
Genomic Research ◽  
Go Annotation ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Mirnas Expression ◽  
Paired End Sequencing

The budgerigar (Melopsittacus undulatus) is one of the most widely studied parrot species, serving as an excellent animal model for behavior and neuroscience research. Until recently, it was unknown how sexual differences in the behavior, physiology, and development of organisms are regulated by differential gene expression. MicroRNAs (miRNAs) are endogenous short non-coding RNA molecules that can post-transcriptionally regulate gene expression and play a critical role in gonadal differentiation as well as early development of animals. However, very little is known about the role gonadal miRNAs play in the early development of birds. Research on the sex-biased expression of miRNAs in avian gonads are limited, and little is known aboutM. undulatus. In the current study, we sequenced two small non-coding RNA libraries made from the gonads of adult male and female budgerigars using Illumina paired-end sequencing technology. We obtained 254 known and 141 novel miRNAs, and randomly validated five miRNAs. Of these, three miRNAs were differentially expressed miRNAs and 18 miRNAs involved in sexual differentiation as determined by functional analysis with GO annotation and KEGG pathway analysis. In conclusion, this work is the first report of sex-biased miRNAs expression in the budgerigar, and provides additional sequences to the avian miRNAome database which will foster further functional genomic research.

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