scholarly journals Control of human testis-specific gene expression

2019 ◽  
Author(s):  
Jay C. Brown
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Start Site ◽  
Binding Sites ◽  
Human Testis ◽  
Specific Gene ◽  
Start Site ◽  
Transcription Start ◽  
Control Of Gene Expression ◽  
Differentiated Cells

AbstractBackgroundAs a result of decades of effort by many investigators we now have an advanced level of understanding about several molecular systems involved in the control of gene expression. Examples include CpG islands, promoters, mRNA splicing and epigenetic signals. It is less clear, however, how such systems work together to integrate the functions of a living organism. Here I describe the results of a study to test the idea that a contribution might be made by focusing on genes specifically expressed in a particular tissue, the human testis.Experimental DesignA database of 239 testis-specific genes was accumulated and each was examined for the presence of features relevant to control of gene expression. These include: (1) the presence of a promoter, (2) the presence of a CpG island (CGI) within the promoter, (3) the presence in the promoter of a transcription factor binding site near the transcription start site, (4) the level of gene expression, and (5) the above features in genes of cell types such as spermatocyte and spermatid that differ in their extent of differentiation.ResultsOf the 107 database genes with an annotated promoter, 56 were found to have one or more transcription factor binding sites near the transcription start site. Three of the binding sites observed, Pax-5, AP-2αA and GRα, stand out in abundance suggesting they may be involved in testis-specific gene expression. Compared to less differentiated testis-specific cells, genes of more differentiated cells were found to be (1) more likely to lack a CGI, (2) more likely to lack introns and (3) higher in expression level. The results suggest genes of more differentiated cells have a reduced need for CGI-based regulatory repression, reduced usage of gene splicing and a smaller set of expressed proteins

scholarly journals Contributions of UP Elements and the Transcription Factor FIS to Expression from the Seven rrn P1 Promoters inEscherichia coli

2001 ◽  
Vol 183 (21) ◽  
pp. 6305-6314 ◽  
Author(s):  
Christine A. Hirvonen ◽  
Wilma Ross ◽  
Christopher E. Wozniak ◽  
Erin Marasco ◽  
Jennifer R. Anthony ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
Promoter Activity ◽  
The Other ◽  
Multigene Families ◽  
Inescherichia Coli ◽  
Start Site ◽  
Transcription Start ◽  
Control Of Gene Expression ◽  
Up Elements

ABSTRACT The high activity of the rrnB P1 promoter inEscherichia coli results from acis-acting DNA sequence, the UP element, and atrans-acting transcription factor, FIS. In this study, we examine the effects of FIS and the UP element at the other sixrrn P1 promoters. We find that UP elements are present at all of the rrn P1 promoters, but they make different relative contributions to promoter activity. Similarly, FIS binds upstream of, and activates, all seven rrn P1 promoters but to different extents. The total number of FIS binding sites, as well as their positions relative to the transcription start site, differ at each rrn P1 promoter. Surprisingly, the FIS sites upstream of site I play a much larger role in transcription from most rrn P1 promoters compared to rrnBP1. Our studies indicate that the overall activities of the sevenrrn P1 promoters are similar, and the same contributors are responsible for these high activities, but these inputs make different relative contributions and may act through slightly different mechanisms at each promoter. These studies have implications for the control of gene expression of unlinked multigene families.

scholarly journals Transcription factor abundance controlled by an auto-regulatory mechanism involving a transcription start site switch

2013 ◽  
Vol 42 (4) ◽  
pp. 2171-2184 ◽  
Author(s):  
Richard Patryk Ngondo ◽  
Philippe Carbon
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Start Site ◽  
Regulatory Mechanism ◽  
Start Site ◽  
Transcription Start ◽  
Aberrant Expression ◽  
Alternative Transcription ◽  
Activating Transcription Factor

Abstract A transcriptional feedback loop is the simplest and most direct means for a transcription factor to provide an increased stability of gene expression. In this work performed in human cells, we reveal a new negative auto-regulatory mechanism involving an alternative transcription start site (TSS) usage. Using the activating transcription factor ZNF143 as a model, we show that the ZNF143 low-affinity binding sites, located downstream of its canonical TSS, play the role of protein sensors to induce the up- or down-regulation of ZNF143 gene expression. We uncovered that the TSS switch that mediates this regulation implies the differential expression of two transcripts with an opposite protein production ability due to their different 5′ untranslated regions. Moreover, our analysis of the ENCODE data suggests that this mechanism could be used by other transcription factors to rapidly respond to their own aberrant expression level.

scholarly journals Location of promoter elements necessary and sufficient to direct testis-specific expression of the Hst70/Hsp70.2 gene

2004 ◽  
Vol 379 (3) ◽  
pp. 739-747 ◽  
Author(s):  
Dorota ŚCIEGLIŃSKA ◽  
Natallia VYDRA ◽  
Zdzisław KRAWCZYK ◽  
Wiesława WIDŁAK
Keyword(s):  
Gene Expression ◽  
Transcription Start Site ◽  
Gene Promoter ◽  
Specific Gene ◽  
Start Site ◽  
Transcription Start ◽  
Mobility Shift ◽  
Specific Expression ◽  
High Level ◽  
Testis Specific Expression

The rat Hst70 gene and its mouse counterpart Hsp70.2 are expressed specifically in pachytene primary spermatocytes and spermatids. Here we demonstrate that a 165 bp fragment of the Hst70 gene promoter, containing the T1 transcription start site region, entire exon 1 and 42 bp 5´ region of the intron, is sufficient to drive testis-specific expression of the chloramphenicol acetyltransferase reporter gene in transgenic mice with the same developmentally regulated pattern as the endogenous Hsp70.2 gene. We show further that high-level tissue-specific gene expression requires additional sequences localized upstream of the T2 transcription start site. Electrophoretic mobility-shift assay analysis revealed that only testes of juvenile rats, when Hst70 gene expression is repressed, contain proteins that specifically bind to the Oct (octamer) sequence localized directly downstream of the T1 site.

scholarly journals Genome-wide identification of enhancers and transcription factors regulating the myogenic differentiation of bovine satellite cells

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Pengcheng Lyu ◽  
Robert E. Settlage ◽  
Honglin Jiang
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Transcription Factors ◽  
Cell Differentiation ◽  
Satellite Cell ◽  
Transcription Start Site ◽  
Satellite Cells ◽  
Binding Sites ◽  
Start Site ◽  
Transcription Start

Abstract Background Satellite cells are the myogenic precursor cells in adult skeletal muscle. The objective of this study was to identify enhancers and transcription factors that regulate gene expression during the differentiation of bovine satellite cells into myotubes. Results Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) was performed to identify genomic regions where lysine 27 of H3 histone is acetylated (H3K27ac), i.e., active enhancers, from bovine satellite cells before and during differentiation into myotubes. A total of 19,027 and 47,669 H3K27ac-marked enhancers were consistently identified from two biological replicates of before- and during-differentiation bovine satellite cells, respectively. Of these enhancers, 5882 were specific to before-differentiation, 35,723 to during-differentiation, and 13,199 common to before- and during-differentiation bovine satellite cells. Whereas most of the before- or during-differentiation-specific H3K27ac-marked enhancers were located distally to the transcription start site, the enhancers common to before- and during-differentiation were located both distally and proximally to the transcription start site. The three sets of H3K27ac-marked enhancers were associated with functionally different genes and enriched with different transcription factor binding sites. Specifically, many of the H3K27ac-marked enhancers specific to during-differentiation bovine satellite cells were associated with genes involved in muscle structure and development, and were enriched with binding sites for the MyoD, AP-1, KLF, TEAD, and MEF2 families of transcription factors. A positive role was validated for Fos and FosB, two AP-1 family transcription factors, in the differentiation of bovine satellite cells into myotubes by siRNA-mediated knockdown. Conclusions Tens of thousands of H3K27ac-marked active enhancers have been identified from bovine satellite cells before or during differentiation. These enhancers contain binding sites not only for transcription factors whose role in satellite cell differentiation is well known but also for transcription factors whose role in satellite cell differentiation is unknown. These enhancers and transcription factors are valuable resources for understanding the complex mechanism that mediates gene expression during satellite cell differentiation. Because satellite cell differentiation is a key step in skeletal muscle growth, the enhancers, the transcription factors, and their target genes identified in this study are also valuable resources for identifying and interpreting skeletal muscle trait-associated DNA variants in cattle.

Decoding the Chromatin Code

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. SCI-4-SCI-4
Author(s):  
Peter A. Jones
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Start Site ◽  
Cpg Islands ◽  
Epigenetic Inheritance ◽  
Promoter Hypermethylation ◽  
Start Site ◽  
Transcription Start ◽  
Control Of Gene Expression ◽  
Transcriptional Start Sites

Abstract Abstract SCI-4 Epigenetic processes are reinforced by interactions between covalent chromatin marks such as DNA methylation, histone modifications, and variants thereof. These marks ultimately specify the locations of nucleosomes, particularly with respect to transcriptional start sites and other regulatory regions. Understanding how the epigenome functions, therefore, requires a coordinated approach in order to reveal the mechanisms by which the chemical modifications interact with nucleosomal remodeling machines to ensure epigenetic inheritance and control of gene expression. We have developed a new methodology to simultaneously map nucleosomal positioning and DNA methylation on individual molecules of DNA. We used this nucleosomal mapping technology to ascertain alterations in nucleosomal positioning during the abnormal silencing of genes by promoter hypermethylation. These experiments show that the methylation of CpG islands at the transcriptional start sites of key tumor-suppressor genes results in the stable placement of nucleosomes at the transcription start site. Treatment with 5-azanucleoside results in an immediate inhibition of DNA methylation and a sequence of downstream events that ultimately result in the eviction of the nucleosomes from the transcription start site and the activation of gene expression. Disclosures: Jones: Eli Lilly: Consultancy.

scholarly journals Sequence of the 5′-flanking region and promoter activity of the human mucin gene MUC5B in different phenotypes of colon cancer cells

2000 ◽  
Vol 348 (3) ◽  
pp. 675-686 ◽  
Author(s):  
Isabelle VAN SEUNINGEN ◽  
Michaël PERRAIS ◽  
Pascal PIGNY ◽  
Nicole PORCHET ◽  
Jean-Pierre AUBERT
Keyword(s):  
Gene Expression ◽  
Transcription Start Site ◽  
Promoter Activity ◽  
Luciferase Reporter ◽  
Nuclear Factor ◽  
Start Site ◽  
Transcription Start ◽  
Mucin Gene ◽  
Intron 1 ◽  
Flanking Region

Control of gene expression in intestinal cells is poorly understood. Molecular mechanisms that regulate transcription of cellular genes are the foundation for understanding developmental and differentiation events. Mucin gene expression has been shown to be altered in many intestinal diseases and especially cancers of the gastrointestinal tract. Towards understanding the transcriptional regulation of a member of the 11p15.5 human mucin gene cluster, we have characterized 3.55 kb of the 5ʹ-flanking region of the human mucin gene MUC5B, including the promoter, the first two exons and the first intron. We report here the promoter activity of successively 5ʹ-truncated sections of 956 bases of this region by fusing it to the coding region of a luciferase reporter gene. The transcription start site was determined by primer-extension analysis. The region upstream of the transcription start site is characterized by the presence of a TATA box at bases -32/-26, DNA-binding elements for transcription factors c-Myc, N-Myc, Sp1 and nuclear factor ĸB as well as putative activator protein (AP)-1-, cAMP-response-element-binding protein (CREB)-, hepatocyte nuclear factor (HNF)-1-, HNF-3-, TGT3-, gut-enriched Krüppel factor (GKLF)-, thyroid transcription factor (TTF)-1- and glucocorticoid receptor element (GRE)-binding sites. Intron 1 of MUC5B was also characterized, it is 2511 nucleotides long and contains a DNA segment of 259 bp in which are clustered eight tandemly repeated GA boxes and a CACCC box that bind Sp1. AP-2α and GATA-1 nuclear factors were also shown to bind to their respective cognate elements in intron 1. In transfection studies the MUC5B promoter showed a cell-specific activity as it is very active in mucus-secreting LS174T cells, whereas it is inactive in Caco-2 enterocytes and HT-29 STD (standard) undifferentiated cells. Within the promoter, maximal transcription activity was found in a segment covering the first 223 bp upstream of the transcription start site. Finally, in co-transfection experiments a transactivating effect of Sp1 on to MUC5B promoter was seen in LS174T and Caco-2 cells.

scholarly journals Influence of cis Element Arrangement on Promoter Strength in Trichoderma reesei

2017 ◽  
Vol 84 (1) ◽  
Author(s):  
Daniel P. Kiesenhofer ◽  
Robert L. Mach ◽  
Astrid R. Mach-Aigner
Keyword(s):  
Trichoderma Reesei ◽  
Transcription Start Site ◽  
Binding Sites ◽  
Inverted Repeat ◽  
Promoter Activity ◽  
Promoter Strength ◽  
Start Site ◽  
Transcription Start ◽  
Content Type ◽  
Sheer Number

ABSTRACTTrichoderma reeseican produce up to 100 g/liter of extracellular proteins. The major and industrially relevant products are cellobiohydrolase I (CBHI) and the hemicellulase XYNI. The genes encoding both enzymes are transcriptionally activated by the regulatory protein Xyr1. The first 850 nucleotides of thecbh1promoter contain 14 Xyr1-binding sites (XBS), and 8 XBS are present in thexyn1promoter. Some of these XBS are arranged in tandem and others as inverted repeats. One suchciselement, an inverted repeat, plays a crucial role in the inducibility of thexyn1promoter. We investigated the impact of the properties of suchciselements by shuffling them by insertion, exchange, deletion, and rearrangement ofciselements in both thecbh1andxyn1promoter. A promoter-reporter assay using theAspergillus nigergoxAgene allowed us to measure changes in the promoter strength and inducibility. Most strikingly, we found that an inverted repeat of XBS causes an important increase incbh1promoter strength and allows induction by xylan or wheat straw. Furthermore, evidence is provided that the distances ofciselements to the transcription start site have important influence on promoter activity. Our results suggest that the arrangement and distances ofciselements have large impacts on the strength of thecbh1promoter, whereas the sheer number of XBS has only secondary importance. Ultimately, the biotechnologically importantcbh1promoter can be improved byciselement rearrangement.IMPORTANCEIn the present study, we demonstrate that the arrangement ofciselements has a major impact on promoter strength and inducibility. We discovered an influence on promoter activity by the distances ofciselements to the transcription start site. Furthermore, we found that the configuration ofciselements has a greater effect on promoter strength than does the sheer number of transactivator binding sites present in the promoter. Altogether, the arrangement ofciselements is an important factor that should not be overlooked when enhancement of gene expression is desired.

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