scholarly journals Comprehensive Expression Profiling of Highly Homologous 39 Hox Genes in 26 Different Human Adult Tissues by the Modified Systematic Multiplex RT-PCR Method Reveals Tissue-Specific Expression Pattern That Suggests an Important Role of Chromosomal Structure in the Regulation of Hox Gene Expression in Adult Tissues

2003 ◽  
Vol 11 (3) ◽  
pp. 199-210 ◽  
Author(s):  
MIYAKO YAMAMOTO ◽  
DAISAKU TAKAI ◽  
FUMIYA YAMAMOTO ◽  
FUMIICHIRO YAMAMOTO
Keyword(s):  
Expression Profiling ◽  
Hox Genes ◽  
Rt Pcr ◽  
Specific Expression ◽  
Chromosomal Structure ◽  
Hox Gene ◽  
Adult Tissues ◽  
Pcr Method ◽  
Specific Expression Pattern

scholarly journals Neuroendocrine prostate cancer has distinctive, non-prostatic HOX code that is represented by the loss of HOXB13 expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Siyuan Cheng ◽  
Shu Yang ◽  
Yingli Shi ◽  
Runhua Shi ◽  
Yunshin Yeh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hox Genes ◽  
Human Cancer ◽  
Specific Expression ◽  
Hox Gene ◽  
Human Cancer Cell Lines ◽  
All Trans Retinoic Acid ◽  
Neuroendocrine Prostate Cancer ◽  
Hox Code ◽  
Specific Expression Pattern

AbstractHOX gene-encoded homeobox proteins control body patterning during embryonic development; the specific expression pattern of HOX genes may correspond to tissue identity. In this study, using RNAseq data of 1019 human cancer cell lines that originated from 24 different anatomic sites, we established HOX codes for various types of tissues. We applied these HOX codes to the transcriptomic profiles of prostate cancer (PCa) samples and found that the majority of prostate adenocarcinoma (AdPCa) samples sustained a prostate-specific HOX code whereas the majority of neuroendocrine prostate cancer (NEPCa) samples did not, which reflects the anaplastic nature of NEPCa. Also, our analysis showed that the NEPCa samples did not correlate well with the HOX codes of any other tissue types, indicating that NEPCa tumors lose their prostate identities but do not gain new tissue identities. Additionally, using immunohistochemical staining, we evaluated the prostatic expression of HOXB13, the most prominently changed HOX gene in NEPCa. We found that HOXB13 was expressed in both benign prostatic tissues and AdPCa but its expression was reduced or lost in NEPCa. Furthermore, we treated PCa cells with all trans retinoic acid (ATRA) and found that the reduced HOXB13 expression can be reverted. This suggests that ATRA is a potential therapeutic agent for the treatment of NEPCa tumors by reversing them to a more treatable AdPCa.

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 APPLICATION OF ELISA-IGM (MAC-ELISA) FOR DETERMINING ETIOLOGICAL LINK VIRUS TYPES IN CONCRET CASES OF THE DISEASE

2017 ◽  
Vol 22 (3) ◽  
pp. 116-121
Author(s):  
Yuliya A. Akinshina ◽  
V. F Larichev ◽  
M. A Sayfullin ◽  
S. G Mardanly ◽  
A. M Butenko
Keyword(s):  
Dengue Fever ◽  
Rt Pcr ◽  
Serum Samples ◽  
Dengue Viruses ◽  
Etiological Role ◽  
Igm Elisa ◽  
Pcr Method

105 sera from 101 patients with a confirmed diagnosis of dengue fever (LD) were examined using monospecific ELISA-IgM test. Monospecific results were observed in 39 samples (37.1%). 27 sample of them were taken during the first 7 days of the disease. In those systems were examined 23 serum samples of 23 patients, in which etiological role of one of the four dengue viruses was been established by the RT-PCR method. In this case, the coincidence-IgM ELISA results and the RT-PCR took place in 14 sera (60.9%).

Gene loss and gain in the evolution of the vertebrates

Development ◽  
1994 ◽  
Vol 1994 (Supplement) ◽  
pp. 155-161
Author(s):  
Frank H. Ruddle ◽  
Kevin L. Bentley ◽  
Michael T. Murtha ◽  
Neil Risch
Keyword(s):  
Hox Genes ◽  
Gene Loss ◽  
Biological Function ◽  
Hox Gene ◽  
Step Process ◽  
Gene Expansion ◽  
Multiple Clusters ◽  
Adaptive Role ◽  
Hox Clusters

Homeobox cluster genes (Hox genes) are highly conserved and can be usefully employed to study phyletic relationships and the process of evolution itself. A phylogenetic survey of Hox genes shows an increase in gene number in some more recently evolved forms, particularly in vertebrates. The gene increase has occurred through a two-step process involving first, gene expansion to form a cluster, and second, cluster duplication to form multiple clusters. We also describe data that suggests that non-Hox genes may be preferrentially associated with the Hox clusters and raise the possibility that this association may have an adaptive biological function. Hox gene loss may also play a role in evolution. Hox gene loss is well substantiated in the vertebrates, and we identify additional possible instances of gene loss in the echinoderms and urochordates based on PCR surveys. We point out the possible adaptive role of gene loss in evolution, and urge the extension of gene mapping studies to relevant species as a means of its substantiation.

The Role of Histone Demethylases in the Transcription Regulation of HOX Genes in PML-RARa+ AML Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 876-876
Author(s):  
Katerina Rejlova ◽  
Karolina Kramarzova ◽  
Meritxell Alberich-Jorda ◽  
Karel Fiser ◽  
Marketa Zaliova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Histone Methylation ◽  
Hox Genes ◽  
Histone Demethylases ◽  
Atra Treatment ◽  
Hox Gene ◽  
Genes Expression ◽  
Methylation Mark

Abstract Homeobox genes (HOX) encode transcription factors that are frequently deregulated in leukemias. Our previous findings described that HOX gene expression differs among genetically characterized subtypes of pediatric AML with PML-RARa+ patients having the lowest overall HOX gene expression. We observed that HOX gene expression positively correlated with expression of histone 3 lysine 27 (H3K27) demethylases JMJD3 and UTX and negatively with DNA methyltransferase DNMT3b. Interestingly, it has been shown that JMJD3 is a direct target of PML-RARa protein (Martens, JH et al, 2010, Cancer Cell). These findings led us to postulate the hypothesis that reduced levels of HOX genes in PML-RARa+ AML can be caused by the suppressed expression of histone demethylases, such as JMJD3 and UTX, resulting in increased H3K27 methylation and transcription inhibition. We chose PML-RARa+ NB4 cell line to study the role of PML-RARa fusion gene in the regulation of HOX gene expression. To inhibit the effect of PML-RARa we used all-trans retinoic acid (ATRA; 1 uM, 10 uM) which was described to release the block caused by this fusion protein. Expression of particular HOX genes (e.g., HOXA1, HOXA3, HOXA5, HOXA7) together with that of JMJD3 and UTX assessed by qPCR was significantly elevated after ATRA treatment, while gene expression of DNMT3b was decreased. To test whether the reduction in HOX gene expression is directly related to the levels of JMJD3 and UTX, we cultured NB4 cells with a specific inhibitor of these histone demethylases, GSK-J4 (1 uM, 10 uM), in combination with ATRA. This co-treatment led to inhibition of JMJD3 and UTX proteins, followed by significant reduction of HOX genes expression (e.g., HOXA1, HOXA3, HOXA5, HOXA7). This result supports our hypothesis that HOX genes expression is directly related to JMJD3/UTX activity. To determine the effect of ATRA and GSK-J4 on histone marks we have isolated histones by acid extraction and detected the levels of histones by western blot in NB4 ATRA or GSK-J4/ATRA treated cells. We observed that the level of repressive histone methylation mark (trimethylated H3K27; H3K27me3) was decreased after ATRA treatment (activation of JMJD3/UTX) and increased after GSK-J4/ATRA co-treatment (inhibition of JMJD3/UTX). The opposite effect was observed in active histone methylation marks where di- and tri-methylated H3K4 (H3K4me2, H3K4me3) increased after ATRA treatment and decreased after GSK-J4/ATRA co-treatment. H3K9 dimethylated (another repressive histone methylation mark) levels did not change. Next, to investigate the histone code directly in particular HOX genes regions we performed chromatin immunoprecipitation (ChIP) assays. We studied the presence of H3K27me3 and H3K4me2 in 5´UTR genomic region of particular HOX genes (HOXA1, HOXA2, HOXA3, HOXA5, HOXA7) in cells treated with ATRA alone or in the combination with GSK-J4. Preliminary results showed reduction in repressive marks (H3K27me3) upon ATRA treatment, whereas addition of GSK-J4 prevented this decrease. Accordingly, we observed that ATRA/GSK-J4 co-treatment reduced active histone mark H3K4me2. To evaluate the role of DNA methylation in observed expression changes after ATRA treatment we performed bisulfite sequencing of particular promoter sites of HOX genes (e.g., HOXA7, HOXA5). Although we detected decreased DNMT3b gene expression after ATRA treatment there was no change in DNA methylation of CpGs in studied regions. Our results demonstrate that changes in chromatin activity correspond with changes in HOX gene expression. Moreover, ChIP data show direct binding of the modified histones and HOX 5´UTR sites. Our data implicate histone demethylases in regulation of HOX gene expression in PML-RARa+ leukemic blasts. DNA methylation in these particular HOX genes is not involved in the regulation. Elucidating the mechanism of regulation of HOX genes expression can help to understand their role in the leukemogenic process. Supported by GACR P304/12/2214 and GAUK 568213. Disclosures No relevant conflicts of interest to declare.

scholarly journals Gene Expression Profiling of Pancreas Neuroendocrine Tumors with Different Ki67-Based Grades

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2054
Author(s):  
Michele Simbolo ◽  
Mirna Bilotta ◽  
Andrea Mafficini ◽  
Claudio Luchini ◽  
Daniela Furlan ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Expression Profiling ◽  
Mutational Analysis ◽  
Expression Profiles ◽  
Tumor Grade ◽  
Proliferation Index ◽  
Specific Expression ◽  
Major Predictor ◽  
Data Call

Pancreatic neuroendocrine tumors (PanNETs) display variable aggressive behavior. A major predictor of survival is tumor grade based on the Ki67 proliferation index. As information on transcriptomic profiles of PanNETs with different tumor grades is limited, we investigated 29 PanNETs (17 G1, 7 G2, 5 G3) for their expression profiles, mutations in 16 PanNET relevant genes and LINE-1 DNA methylation profiles. A total of 3050 genes were differentially expressed between tumors with different grades (p < 0.05): 1279 in G3 vs. G2; 2757 in G3 vs. G1; and 203 in G2 vs. G1. Mutational analysis showed 57 alterations in 11 genes, the most frequent being MEN1 (18/29), DAXX (7/29), ATRX (6/29) and MUTYH (5/29). The presence and type of mutations did not correlate with the specific expression profiles associated with different grades. LINE-1 showed significantly lower methylation in G2/G3 versus G1 tumors (p = 0.007). The expression profiles of matched primaries and metastasis (nodal, hepatic and colorectal wall) of three cases confirmed the role of Ki67 in defining specific expression profiles, which clustered according to tumor grades, independently from anatomic location or patient of origin. Such data call for future exploration of the role of Ki67 in tumor progression, given its involvement in chromosomal stability.

scholarly journals Characterization of the XTH Gene Family: New Insight to the Roles in Soybean Flooding Tolerance

2018 ◽  
Vol 19 (9) ◽  
pp. 2705 ◽  
Author(s):  
Li Song ◽  
Babu Valliyodan ◽  
Silvas Prince ◽  
Jinrong Wan ◽  
Henry Nguyen
Keyword(s):  
Expression Pattern ◽  
Stress Responses ◽  
Germination Rate ◽  
Gene Expression Pattern ◽  
Growth Stages ◽  
Flooding Tolerance ◽  
Specific Expression ◽  
Flooding Stress ◽  
Specific Expression Pattern

Xyloglucan endotransglycosylases/hydrolases (XTHs) are a class of enzymes involved in the construction and remodeling of cellulose/xyloglucan crosslinks and play an important role in regulating cell wall extensibility. However, little is known about this class of enzymes in soybean. Here, 61 soybean XTH genes (GmXTHs) were identified and classified into three subgroups through comparative phylogenetic analysis. Genome duplication greatly contributed to the expansion of GmXTH genes in soybean. A conserved amino acid motif responsible for the catalytic activity was identified in all GmXTHs. Further expression analysis revealed that most GmXTHs exhibited a distinct organ-specific expression pattern, and the expression level of many GmXTH genes was significantly associated with ethylene and flooding stress. To illustrate a possible role of XTH genes in regulating stress responses, the Arabidopsis AtXTH31 gene was overexpressed in soybean. The generated transgenic plants exhibited improved tolerance to flooding stress, with a higher germination rate and longer roots/hypocotyls during the seedling stage and vegetative growth stages. In summary, our combined bioinformatics and gene expression pattern analyses suggest that GmXTH genes play a role in regulating soybean stress responses. The enhanced soybean flooding tolerance resulting from the expression of an Arabidopsis XTH also supports the role of XTH genes in regulating plant flooding stress responses.

HOX Genes - Candidate Tumor Suppressor Genes in Adult and Childhood Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2641-2641
Author(s):  
Gordon R. Strathdee ◽  
Tessa L. Holyoake ◽  
Alyson Sim ◽  
Anton Parker ◽  
David G. Oscier ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Gene Family ◽  
Tumor Suppressor Genes ◽  
Poor Prognosis ◽  
Childhood Leukemia ◽  
Hox Genes ◽  
Blast Crisis ◽  
Family Members ◽  
Hox Gene

Abstract The role of the HOX gene family in leukemia development has been extensively studied. However, these studies have focused almost exclusively on the potential oncogenic role of HOX gene family members. In contrast to the oncogenic function often attributed to HOX genes, our studies have identified several HOX gene family members as candidate tumor suppressor genes and shown that inactivation of HOX genes, particularly HOXA4, is associated with poor prognosis. We have used multiple quantitative methylation assays to search for epigenetic inactivation of HOX genes in adult and childhood leukemia. In both adult myeloid and lymphoid leukemia two members of the HOXA cluster (HOXA4 and A5) were found to be frequently inactivated by promoter hypermethylation (26–64% of cases were hypermethylated). In contrast, a further 12 HOXA, B and C cluster genes were found to be essentially devoid of hypermethylation (except HOXA6 in CLL, where 34% of samples exhibited hypermethylation). HOXA4 and HOXA5 were also frequently inactivated in childhood ALL and AML (39–79% of samples). However, in contrast to the adult leukemias, all but one of the additional HOX genes analyzed were also found to be targets for hypermethylation in both ALL and AML (4–26% of samples), suggesting that HOX genes are differentially regulated in childhood versus adult leukemia. Hypermethylation of HOX genes (HOXA4, HOXA5 and HOXA6) was associated with loss of expression of the corresponding gene. Expression analysis also suggests that interaction between different HOX genes may be crucial. In normal karyotype AML samples, those expressing of high levels of HOXA9, but not those with low HOXA9 expression, were associated with invariable HOXA4 hypermethylation (p=0.01). Interestingly HOXA4 hypermethylation also correlates with poor prognosis in all types of leukemia tested. Hypermethylation of HOXA4 correlates with progression to blast crisis (p=0.007) and poor response to imatinib in CML (p=0.04), with cytogenetic status in AML (33%, 72% and 100% in good, intermediate and poor prognostic groups respectively, p=0.0004) and with IgVh mutational status (p=0.003) and poor survival in CLL (median survival 159 versus 199 months in hypermethylated and non hypermethylated patients, respectively). Furthermore transfection of a HOXA4 expressing construct into a CML blast crisis cell line results in re-expression of markers of myeloid differentiation, suggesting that loss of HOXA4 is functionally relevant in leukemic cells. These results indicate that aberrant epigenetic regulation of HOXA4, and indeed other frequently inactivated HOX genes such as HOXA5 and HOXA6, may play a key role in the development of multiple types of leukemia. Thus co-ordinated up and down regulation of expression of HOX gene family members may be crucial in the leukemogenic process.

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