scholarly journals The constrained architecture of mammalian Hox gene clusters

2019 ◽  
Vol 116 (27) ◽  
pp. 13424-13433 ◽  
Author(s):  
Fabrice Darbellay ◽  
Célia Bochaton ◽  
Lucille Lopez-Delisle ◽  
Bénédicte Mascrez ◽  
Patrick Tschopp ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Target Genes ◽  
Gene Clusters ◽  
Genetic System ◽  
Bilateral Symmetry ◽  
Vertebrate Lineage ◽  
Global Gene Regulation ◽  
Functional Relevance ◽  
Dna Strand ◽  
Ctcf Site

In many animal species with a bilateral symmetry, Hox genes are clustered either at one or at several genomic loci. This organization has a functional relevance, as the transcriptional control applied to each gene depends upon its relative position within the gene cluster. It was previously noted that vertebrate Hox clusters display a much higher level of genomic organization than their invertebrate counterparts. The former are always more compact than the latter, they are generally devoid of repeats and of interspersed genes, and all genes are transcribed by the same DNA strand, suggesting that particular factors constrained these clusters toward a tighter structure during the evolution of the vertebrate lineage. Here, we investigate the importance of uniform transcriptional orientation by engineering several alleles within the HoxD cluster, such as to invert one or several transcription units, with or without a neighboring CTCF site. We observe that the association between the tight structure of mammalian Hox clusters and their regulation makes inversions likely detrimental to the proper implementation of this complex genetic system. We propose that the consolidation of Hox clusters in vertebrates, including transcriptional polarity, evolved in conjunction with the emergence of global gene regulation via the flanking regulatory landscapes, to optimize a coordinated response of selected subsets of target genes in cis.

scholarly journals Constrained Transcriptional Polarity in the Organization of MammalianHoxGene Clusters

2019 ◽  
Author(s):  
Fabrice Darbellay ◽  
Célia Bochaton ◽  
Lucille Lopez-Delisle ◽  
Bénédicte Mascrez ◽  
Patrick Tschopp ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Target Genes ◽  
Genetic System ◽  
Bilateral Symmetry ◽  
Transcription Unit ◽  
Vertebrate Lineage ◽  
Global Gene Regulation ◽  
Functional Relevance ◽  
Dna Strand ◽  
Ctcf Site

ABSTRACTIn many animal species with a bilateral symmetry,Hoxgenes are clustered either at one or at several genomic loci. This organization has a functional relevance, as the transcriptional control applied to each gene depends upon its relative position within the gene cluster. It was previously noted that vertebrateHoxclusters display a much higher level of genomic organization than their invertebrate counterparts. The former are always more compact than the latter, they are generally devoid of repeats and of interspersed genes, and all genes are transcribed by the same DNA strand, suggesting that particular factors constrained these clusters towards a tighter structure during the evolution of the vertebrate lineage. Here we investigate the importance of uniform transcriptional orientation by engineering several alleles within theHoxDcluster such as to invert one or several transcription unit(s), with or without a neighboring CTCF site. We observe that the association between the tight structure of mammalianHoxclusters and their regulation makes inversions likely detrimental to the proper implementation of this complex genetic system. We propose that the consolidation ofHoxclusters in vertebrates, including transcriptional polarity, evolved in conjunction with the emergence of global gene regulationviathe flanking regulatory landscapes, to optimize a coordinated response of selected subsets of target genes incis.

scholarly journals Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tatsuya Shimizu ◽  
Naomasa Fujita ◽  
Kiyomi Tsuji-Tamura ◽  
Yoshimasa Kitagawa ◽  
Toshiaki Fujisawa ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Transcriptional Control ◽  
Target Genes ◽  
Pulsed Ultrasound ◽  
Activated T Cells ◽  
In Vivo Models ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity ◽  
Ultrasound Stimulation

AbstractUltrasound stimulation is a type of mechanical stress, and low-intensity pulsed ultrasound (LIPUS) devices have been used clinically to promote fracture healing. However, it remains unclear which skeletal cells, in particular osteocytes or osteoblasts, primarily respond to LIPUS stimulation and how they contribute to fracture healing. To examine this, we utilized medaka, whose bone lacks osteocytes, and zebrafish, whose bone has osteocytes, as in vivo models. Fracture healing was accelerated by ultrasound stimulation in zebrafish, but not in medaka. To examine the molecular events induced by LIPUS stimulation in osteocytes, we performed RNA sequencing of a murine osteocytic cell line exposed to LIPUS. 179 genes reacted to LIPUS stimulation, and functional cluster analysis identified among them several molecular signatures related to immunity, secretion, and transcription. Notably, most of the isolated transcription-related genes were also modulated by LIPUS in vivo in zebrafish. However, expression levels of early growth response protein 1 and 2 (Egr1, 2), JunB, forkhead box Q1 (FoxQ1), and nuclear factor of activated T cells c1 (NFATc1) were not altered by LIPUS in medaka, suggesting that these genes are key transcriptional regulators of LIPUS-dependent fracture healing via osteocytes. We therefore show that bone-embedded osteocytes are necessary for LIPUS-induced promotion of fracture healing via transcriptional control of target genes, which presumably activates neighboring cells involved in fracture healing processes.

scholarly journals Functional expression of a vertebrate inwardly rectifying K+ channel in yeast.

1995 ◽  
Vol 6 (9) ◽  
pp. 1231-1240 ◽  
Author(s):  
W Tang ◽  
A Ruknudin ◽  
W P Yang ◽  
S Y Shaw ◽  
A Knickerbocker ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Xenopus Oocytes ◽  
Genetic System ◽  
Functional Expression ◽  
Inward Rectifier ◽  
K Channel ◽  
Coding Region ◽  
Low Potassium ◽  
K Current ◽  
Inwardly Rectifying

We describe the expression of gpIRK1, an inwardly rectifying K+ channel obtained from guinea pig cardiac cDNA. gpIRK1 is a homologue of the mouse IRK1 channel identified in macrophage cells. Expression of gpIRK1 in Xenopus oocytes produces inwardly rectifying K+ current, similar to the cardiac inward rectifier current IK1. This current is blocked by external Ba2+ and Cs+. Plasmids containing the gpIRK1 coding region under the transcriptional control of constitutive (PGK) or inducible (GAL) promoters were constructed for expression in Saccharomyces cerevisiae. Several observations suggest that gpIRK1 forms functional ion channels when expressed in yeast. gpIRK1 complements a trk1 delta trk2 delta strain, which is defective in potassium uptake. Expression of gpIRK1 in this mutant restores growth on low potassium media. Growth dependent on gpIRK1 is inhibited by external Cs+. The strain expressing gpIRK1 provides a versatile genetic system for studying the assembly and composition of inwardly rectifying K+ channels.

scholarly journals Co-activator SRC-1 is dispensable for transcriptional control by STAT3

2009 ◽  
Vol 420 (1) ◽  
pp. 123-132 ◽  
Author(s):  
Helena Cvijic ◽  
Kay Bauer ◽  
Dennis Löffler ◽  
Gabriele Pfeifer ◽  
Conny Blumert ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Target Genes ◽  
Binding Protein ◽  
Myeloma Cell ◽  
Camp Response Element Binding ◽  
Signal Transducer ◽  
Il Interleukin ◽  
Element Binding Protein ◽  
Induced Apoptosis ◽  
Microarray Expression

SRC (steroid receptor co-activator)-1 has been reported to interact with and to be an essential co-activator for several members of the STAT (signal transducer and activator of transcription) family, including STAT3, the major signal transducer of IL (interleukin)-6. We addressed the question of whether SRC-1 is crucial for IL-6- and STAT3-mediated physiological responses such as myeloma cell survival and acute-phase protein induction. In fact, silencing of SRC-1 by RNA interference rapidly induced apoptosis in IL-6-dependent INA-6 human myeloma cells, comparable with what was observed upon silencing of STAT3. Using chromatin immunoprecipitation at STAT3 target regions of various genes, however, we observed constitutive binding of SRC-1 that decreased when INA-6 cells were treated with IL-6. The same held true for STAT3 target genes analysed in HepG2 human hepatocellular carcinoma cells. SRC-1-knockdown studies demonstrated that STAT3-controlled promoters require neither SRC-1 nor the other p160 family members SRC-2 or SRC-3 in HepG2 cells. Furthermore, microarray expression profiling demonstrated that the responsiveness of IL-6 target genes is not affected by SRC-1 silencing. In contrast, co-activators of the CBP [CREB (cAMP-response element-binding protein)-binding protein]/p300 family proved functionally important for the transactivation potential of STAT3 and bound inducibly to STAT3 target regions. This recruitment did not depend on the presence of SRC-1. Altogether, this suggests that functional impairment of STAT3 is not involved in the induction of myeloma cell apoptosis by SRC-1 silencing. We therefore conclude that STAT3 transactivates its target genes by the recruitment of CBP/p300 co-activators and that this process generally does not require the contribution of SRC-1.

scholarly journals The Class III Peroxidase (POD) Gene Family in Cassava: Identification, Phylogeny, Duplication, and Expression

2019 ◽  
Vol 20 (11) ◽  
pp. 2730 ◽  
Author(s):  
Chunlai Wu ◽  
Xupo Ding ◽  
Zehong Ding ◽  
Weiwei Tie ◽  
Yan Yan ◽  
...  
Keyword(s):  
Stress Responses ◽  
Transcriptional Control ◽  
Tandem Duplication ◽  
Target Genes ◽  
Hormone Signaling ◽  
Class Iii ◽  
Motif Analysis ◽  
Transcriptional Changes ◽  
Postharvest Physiological Deterioration ◽  
Class Iii Peroxidase

The class III peroxidase (POD) enzymes participate in plant development, hormone signaling, and stress responses. However, little is known about the POD family in cassava. Here, we identified 91 cassava POD genes (MePODs) and classified them into six subgroups using phylogenetic analysis. Conserved motif analysis demonstrated that all MePOD proteins have typical peroxidase domains, and gene structure analysis showed that MePOD genes have between one and nine exons. Duplication pattern analysis suggests that tandem duplication has played a role in MePOD gene expansion. Comprehensive transcriptomic analysis revealed that MePOD genes in cassava are involved in the drought response and postharvest physiological deterioration. Several MePODs underwent transcriptional changes after various stresses and related signaling treatments were applied. In sum, we characterized the POD family in cassava and uncovered the transcriptional control of POD genes in response to various stresses and postharvest physiological deterioration conditions. These results can be used to identify potential target genes for improving the stress tolerance of cassava crops.

scholarly journals MiR-146a/b: a family with shared seeds and different roots

2017 ◽  
Vol 49 (4) ◽  
pp. 243-252 ◽  
Author(s):  
Mark R. Paterson ◽  
Alison J. Kriegel
Keyword(s):  
Target Genes ◽  
Family Members ◽  
Differential Regulation ◽  
Seed Region ◽  
Small Noncoding Rnas ◽  
Specific Effects ◽  
Exciting Potential ◽  
Health And Disease ◽  
Experimental Approaches ◽  
Functional Relevance

MicroRNAs are small, noncoding, RNAs known for their powerful modulation of molecular processes, making them a major focus for studying pathological mechanisms. The human miR-146 family of microRNAs consists of two member genes, MIR146A and MIR146B. These two microRNAs are located on different chromosomes and exhibit differential regulation in many cases. However, they are nearly identical in sequence, sharing a seed region, and are thus predicted to target the same set of genes. A large proportion of the microRNA (miR)-146 literature focuses on its role in regulating the innate immune response in the context of various pathologies by modulating two widely studied target genes in the toll-like receptor signaling cascade. A growing subset of the literature reports a role of miR-146 in cardiovascular and renal disease, and data suggest there is exciting potential for miR-146 as a diagnostic and therapeutic target. Nevertheless, the published literature is confounded by unclear and imprecise language concerning the specific effects of the two miR-146 family members. The present review will compare the genomic origin and regulation of miR-146a and miR-146b, discuss some approaches to overcome analytical and experimental challenges, and summarize findings in major areas of miR-146 research. Moving forward, careful evaluation of miR-146a/b specificity in analytical and experimental approaches will aid researchers in elucidating the functional relevance of differential regulation of the miR-146 family members in health and disease.

scholarly journals Characterization of Three Small Proteins inBrucella abortusLinked to Fucose Utilization

2018 ◽  
Vol 200 (18) ◽  
Author(s):  
James A. Budnick ◽  
Lauren M. Sheehan ◽  
Lin Kang ◽  
Pawel Michalak ◽  
Clayton C. Caswell
Keyword(s):  
Brucella Abortus ◽  
Transcriptional Control ◽  
Sugar Transport ◽  
Genetic System ◽  
Growth Conditions ◽  
Content Type ◽  
Small Regulatory Rna ◽  
Small Proteins

ABSTRACTElucidating the function of proteins <50 amino acids in length is no small task. Nevertheless, small proteins can play vital roles in the lifestyle of bacteria and influence the virulence of pathogens; thus, the investigation of the small proteome is warranted. Recently, our group identified theBrucella abortusprotein VtlR as a transcriptional activator of four genes, one of which is the well-studied small regulatory RNA AbcR2, while the other three genes encode hypothetical small proteins, two of which are highly conserved among the orderRhizobiales. This study provides evidence that all three genes encode authentic small proteins and that all three are highly expressed under oxidative stress, low-pH, and stationary-phase growth conditions. Fractionation of the cells revealed that the proteins are localized to the membranes ofB. abortus. We demonstrate that the small proteins under the transcriptional control of VtlR are not accountable for attenuation observed with theB. abortusvtlRdeletion strain. However, there is an association between VtlR-regulated genes and growth inhibition in the presence of the sugarl-fucose. Subsequent transcriptomic analyses revealed thatB. abortusinitiates the transcription of a locus encoding a putative sugar transport and utilization system when the bacteria are cultured in the presence ofl-fucose. Altogether, our observations characterize the role of the VtlR-controlled small proteins BAB1_0914, BAB2_0512, and BAB2_0574 in the biology ofB. abortus, particularly in the capacity of the bacteria to utilizel-fucose.IMPORTANCEDespite being one of the most common zoonoses worldwide, there is currently no human vaccine to combat brucellosis. Therefore, a better understanding of the pathogenesis and biology ofBrucellaspp., the causative agent of brucellosis, is essential for the discovery of novel therapeutics against these highly infectious bacteria. In this study, we further characterize the virulence-associated transcriptional regulator VtlR inBrucella abortus. Our findings not only shed light on our current understanding of a virulence related genetic system inBrucellaspp. but also increase our knowledge of small proteins in the field of bacteriology.

Next generation sequencing allows deeper analysis and understanding of genomes and transcriptomes including aspects to fertility

2011 ◽  
Vol 23 (1) ◽  
pp. 75 ◽  
Author(s):  
Thomas Werner
Keyword(s):  
Next Generation Sequencing ◽  
Transcriptional Control ◽  
Target Genes ◽  
De Novo ◽  
Alternative Promoters ◽  
Next Generation ◽  
Sequencing Data ◽  
Genome Wide ◽  
A Genome ◽  
Generation Sequencing

Reproduction and fertility are controlled by specific events naturally linked to oocytes, testes and early embryonal tissues. A significant part of these events involves gene expression, especially transcriptional control and alternative transcription (alternative promoters and alternative splicing). While methods to analyse such events for carefully predetermined target genes are well established, until recently no methodology existed to extend such analyses into a genome-wide de novo discovery process. With the arrival of next generation sequencing (NGS) it becomes possible to attempt genome-wide discovery in genomic sequences as well as whole transcriptomes at a single nucleotide level. This does not only allow identification of the primary changes (e.g. alternative transcripts) but also helps to elucidate the regulatory context that leads to the induction of transcriptional changes. This review discusses the basics of the new technological and scientific concepts arising from NGS, prominent differences from microarray-based approaches and several aspects of its application to reproduction and fertility research. These concepts will then be illustrated in an application example of NGS sequencing data analysis involving postimplantation endometrium tissue from cows.

scholarly journals Neuronal Activation of NF-κB Contributes to Cell Death in Cerebral Ischemia

2005 ◽  
Vol 25 (1) ◽  
pp. 30-40 ◽  
Author(s):  
Wen Zhang ◽  
Ioana Potrovita ◽  
Victoria Tarabin ◽  
Oliver Herrmann ◽  
Verena Beer ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Cortical Neurons ◽  
Transcriptional Control ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Neuron Specific Enolase ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion

The transcription factor NF-κB is a key regulator of inflammation and cell survival. NF-κB is activated by cerebral ischemia in neurons and glia, but its function is controversial. To inhibit NF-κB selectively in neurons and glial cells, we have generated transgenic mice that express the IκBα superrepressor (IκBα mutated at serine-32 and serine-36, IκBα-SR) under transcriptional control of the neuron-specific enolase (NSE) and the glial fibrillary acidic protein (GFAP) promoter, respectively. In primary cortical neurons of NSE-IκBα-SR mice, NF-κB activity was partially inhibited. To assess NF-κB activity in vivo after permanent middle cerebral artery occlusion (MCAO), we measured the expression of NF-κB target genes by real-time polymerase chain reaction (PCR). The induction of c-myc and transforming growth factor-β2 by cerebral ischemia was inhibited by neuronal expression of IκBα-SR, whereas induction of GFAP by MCAO was reduced by astrocytic expression of IκBα-SR. Neuronal, but not astrocytic, expression of the NF-κB inhibitor reduced both infarct size and cell death 48 hours after permanent MCAO. In summary, the data show that NF-κB is activated in neurons and astrocytes during cerebral ischemia and that NF-κB activation in neurons contributes to the ischemic damage.

scholarly journals Differential Regulation of Foxo3a Target Genes in Erythropoiesis

2007 ◽  
Vol 27 (10) ◽  
pp. 3839-3854 ◽  
Author(s):  
Walbert J. Bakker ◽  
Thamar B. van Dijk ◽  
Martine Parren-van Amelsvoort ◽  
Andrea Kolbus ◽  
Kazuo Yamamoto ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Target Genes ◽  
Erythroid Differentiation ◽  
Erythroid Progenitors ◽  
Jun Kinase ◽  
Growth Inhibitory Factor ◽  
Growth Inhibitory ◽  
Target Regulation ◽  
Stimulatory Factor ◽  
Erythroid Development

ABSTRACT The cooperation of stem cell factor (SCF) and erythropoietin (Epo) is required to induce renewal divisions in erythroid progenitors, whereas differentiation to mature erythrocytes requires the presence of Epo only. Epo and SCF activate common signaling pathways such as the activation of protein kinase B (PKB) and the subsequent phosphorylation and inactivation of Foxo3a. In contrast, only Epo activates Stat5. Both Foxo3a and Stat5 promote erythroid differentiation. To understand the interplay of SCF and Epo in maintaining the balance between renewal and differentiation during erythroid development, we investigated differential Foxo3a target regulation by Epo and SCF. Expression profiling revealed that a subset of Foxo3a targets was not inhibited but was activated by Epo. One of these genes was Cited2. Transcriptional control of Epo/Foxo3a-induced Cited2 was studied and compared with that of the Epo-repressed Foxo3a target Btg1. We show that in response to Epo, the allegedly growth-inhibitory factor Foxo3a associates with the allegedly growth-stimulatory factor Stat5 in the nucleus, which is required for Epo-induced Cited2 expression. In contrast, Btg1 expression is controlled by the cooperation of Foxo3a with cyclic AMP- and Jun kinase-dependent Creb family members. Thus, Foxo3a not only is an effector of PKB but also integrates distinct signals to regulate gene expression in erythropoiesis.

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