Binding Sites in theEFG1Promoter for Transcription Factors in a Proposed Regulatory Network: A Functional Analysis in the White and Opaque Phases ofCandida albicans

ABSTRACT In the model eukaryote Saccharomyces cerevisiae , the transcription factor Cst6p has been reported to play important roles in several biological processes. However, the genome-wide targets of Cst6p and its physiological functions remain unknown. Here, we mapped the genome-wide binding sites of Cst6p at high resolution. Cst6p binds to the promoter regions of 59 genes with various biological functions when cells are grown on ethanol but hardly binds to the promoter at any gene when cells are grown on glucose. The retarded growth of the CST6 deletion mutant on ethanol is attributed to the markedly decreased expression of NCE103 , encoding a carbonic anhydrase, which is a direct target of Cst6p. The target genes of Cst6p have a large overlap with those of stress-responsive transcription factors, such as Sko1p and Skn7p. In addition, a CST6 deletion mutant growing on ethanol shows hypersensitivity to oxidative stress and ethanol stress, assigning Cst6p as a new member of the stress-responsive transcriptional regulatory network. These results show that mapping of genome-wide binding sites can provide new insights into the function of transcription factors and highlight the highly connected and condition-dependent nature of the transcriptional regulatory network in S. cerevisiae . IMPORTANCE Transcription factors regulate the activity of various biological processes through binding to specific DNA sequences. Therefore, the determination of binding positions is important for the understanding of the regulatory effects of transcription factors. In the model eukaryote Saccharomyces cerevisiae , the transcription factor Cst6p has been reported to regulate several biological processes, while its genome-wide targets remain unknown. Here, we mapped the genome-wide binding sites of Cst6p at high resolution. We show that the binding of Cst6p to its target promoters is condition dependent and explain the mechanism for the retarded growth of the CST6 deletion mutant on ethanol. Furthermore, we demonstrate that Cst6p is a new member of a stress-responsive transcriptional regulatory network. These results provide deeper understanding of the function of the dynamic transcriptional regulatory network in S. cerevisiae .

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Evolutionary rewiring of the human regulatory network by waves of genome expansion

10.1101/164434 ◽

2017 ◽

Author(s):

Davide Marnetto ◽

Federica Mantica ◽

Ivan Molineris ◽

Elena Grassi ◽

Igor Pesando ◽

...

Keyword(s):

Transcription Factors ◽

Binding Sites ◽

Regulatory Network ◽

Genomic Sequence ◽

Age Distribution ◽

Point Mutations ◽

Regulatory Elements ◽

Functional Regions ◽

Genome Expansion ◽

Evolution Of Gene Regulation

AbstractGenome expansion is believed to be an important driver of the evolution of gene regulation. To investigate the role of newly arising sequence in rewiring the regulatory network we estimated the age of each region of the human genome by applying maximum parsimony to genome-wide alignments with 100 vertebrates. We then studied the age distribution of several types of functional regions, with a focus on regulatory elements. The age distribution of regulatory elements reveals the extensive use of newly formed genomic sequence in the evolution of regulatory interactions. Many transcription factors have expanded their repertoire of targets through waves of genomic expansions that can be traced to specific evolutionary times. Repeated elements contributed a major part of such expansion: many classes of such elements are enriched in binding sites of one or a few specific transcription factors, whose binding sites are localized in specific portions of the element and characterized by distinctive motif words. These features suggest that the binding sites were available as soon as the new sequence entered the genome, rather than being created later by accumulation of point mutations. By comparing the age of regulatory regions to the evolutionary shift in expression of nearby genes we show that rewiring through genome expansion played an important role in shaping the human regulatory network.

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Faculty Opinions recommendation of TNIP1 reduction of HSPA6 gene expression occurs in promoter regions lacking binding sites for known TNIP1-repressed transcription factors.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725258444.793503625 ◽

2015 ◽

Author(s):

Sarah Gaffen ◽

J Agustin Cruz

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Binding Sites ◽

Promoter Regions

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Comparative analysis of conservation and regulatory network on core transcription factors in mouse inner ear development

Hereditas (Beijing) ◽

10.3724/sp.j.1005.2013.01198 ◽

2013 ◽

Vol 35 (10) ◽

pp. 1198-1208

Author(s):

Zhi-Qiang CHEN ◽

Xin-Huan HAN ◽

Qin-Jun WEI ◽

Guang-Qian XING ◽

Xin CAO

Keyword(s):

Transcription Factors ◽

Comparative Analysis ◽

Inner Ear ◽

Regulatory Network ◽

Ear Development ◽

Inner Ear Development

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NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22115902 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5902

Author(s):

Stefan Nagel ◽

Claudia Pommerenke ◽

Corinna Meyer ◽

Hans G. Drexler

Keyword(s):

Dendritic Cells ◽

Transcription Factors ◽

Cell Lines ◽

Expression Profiling ◽

Regulatory Network ◽

Homeobox Gene ◽

Leukemia Cell Line ◽

Specific Gene ◽

Rna Seq ◽

And Function

Recently, we documented a hematopoietic NKL-code mapping physiological expression patterns of NKL homeobox genes in human myelopoiesis including monocytes and their derived dendritic cells (DCs). Here, we enlarge this map to include normal NKL homeobox gene expressions in progenitor-derived DCs. Analysis of public gene expression profiling and RNA-seq datasets containing plasmacytoid and conventional dendritic cells (pDC and cDC) demonstrated HHEX activity in both entities while cDCs additionally expressed VENTX. The consequent aim of our study was to examine regulation and function of VENTX in DCs. We compared profiling data of VENTX-positive cDC and monocytes with VENTX-negative pDC and common myeloid progenitor entities and revealed several differentially expressed genes encoding transcription factors and pathway components, representing potential VENTX regulators. Screening of RNA-seq data for 100 leukemia/lymphoma cell lines identified prominent VENTX expression in an acute myelomonocytic leukemia cell line, MUTZ-3 containing inv(3)(q21q26) and t(12;22)(p13;q11) and representing a model for DC differentiation studies. Furthermore, extended gene analyses indicated that MUTZ-3 is associated with the subtype cDC2. In addition to analysis of public chromatin immune-precipitation data, subsequent knockdown experiments and modulations of signaling pathways in MUTZ-3 and control cell lines confirmed identified candidate transcription factors CEBPB, ETV6, EVI1, GATA2, IRF2, MN1, SPIB, and SPI1 and the CSF-, NOTCH-, and TNFa-pathways as VENTX regulators. Live-cell imaging analyses of MUTZ-3 cells treated for VENTX knockdown excluded impacts on apoptosis or induced alteration of differentiation-associated cell morphology. In contrast, target gene analysis performed by expression profiling of knockdown-treated MUTZ-3 cells revealed VENTX-mediated activation of several cDC-specific genes including CSFR1, EGR2, and MIR10A and inhibition of pDC-specific genes like RUNX2. Taken together, we added NKL homeobox gene activities for progenitor-derived DCs to the NKL-code, showing that VENTX is expressed in cDCs but not in pDCs and forms part of a cDC-specific gene regulatory network operating in DC differentiation and function.

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Regulatory Network Analysis in Estradiol-Treated Human Endothelial Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22158193 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8193

Author(s):

Daniel Pérez-Cremades ◽

Ana B. Paes ◽

Xavier Vidal-Gómez ◽

Ana Mompeón ◽

Carlos Hermenegildo ◽

...

Keyword(s):

Endothelial Cells ◽

Transcription Factor ◽

Transcription Factors ◽

Regulatory Network ◽

Mirna Target ◽

Target Genes ◽

Functional Characterization ◽

Human Endothelial Cells ◽

Mrna Targets ◽

Canonical Pathways

Background/Aims: Estrogen has been reported to have beneficial effects on vascular biology through direct actions on endothelium. Together with transcription factors, miRNAs are the major drivers of gene expression and signaling networks. The objective of this study was to identify a comprehensive regulatory network (miRNA-transcription factor-downstream genes) that controls the transcriptomic changes observed in endothelial cells exposed to estradiol. Methods: miRNA/mRNA interactions were assembled using our previous microarray data of human umbilical vein endothelial cells (HUVEC) treated with 17β-estradiol (E2) (1 nmol/L, 24 h). miRNA–mRNA pairings and their associated canonical pathways were determined using Ingenuity Pathway Analysis software. Transcription factors were identified among the miRNA-regulated genes. Transcription factor downstream target genes were predicted by consensus transcription factor binding sites in the promoter region of E2-regulated genes by using JASPAR and TRANSFAC tools in Enrichr software. Results: miRNA–target pairings were filtered by using differentially expressed miRNAs and mRNAs characterized by a regulatory relationship according to miRNA target prediction databases. The analysis identified 588 miRNA–target interactions between 102 miRNAs and 588 targets. Specifically, 63 upregulated miRNAs interacted with 295 downregulated targets, while 39 downregulated miRNAs were paired with 293 upregulated mRNA targets. Functional characterization of miRNA/mRNA association analysis highlighted hypoxia signaling, integrin, ephrin receptor signaling and regulation of actin-based motility by Rho among the canonical pathways regulated by E2 in HUVEC. Transcription factors and downstream genes analysis revealed eight networks, including those mediated by JUN and REPIN1, which are associated with cadherin binding and cell adhesion molecule binding pathways. Conclusion: This study identifies regulatory networks obtained by integrative microarray analysis and provides additional insights into the way estradiol could regulate endothelial function in human endothelial cells.

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Multi-omic profiling of pituitary thyrotropic cells and progenitors

BMC Biology ◽

10.1186/s12915-021-01009-0 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Alexandre Z. Daly ◽

Lindsey A. Dudley ◽

Michael T. Peel ◽

Stephen A. Liebhaber ◽

Stephen C. J. Parker ◽

...

Keyword(s):

Transcription Factors ◽

Pituitary Gland ◽

Cell Lines ◽

Binding Sites ◽

Critical Factor ◽

Regulatory Elements ◽

Thyroid Stimulating Hormone ◽

Neuroendocrine Cells ◽

Bzip Transcription Factor ◽

Enhancer Element

Abstract Background The pituitary gland is a neuroendocrine organ containing diverse cell types specialized in secreting hormones that regulate physiology. Pituitary thyrotropes produce thyroid-stimulating hormone (TSH), a critical factor for growth and maintenance of metabolism. The transcription factors POU1F1 and GATA2 have been implicated in thyrotrope fate, but the transcriptomic and epigenomic landscapes of these neuroendocrine cells have not been characterized. The goal of this work was to discover transcriptional regulatory elements that drive thyrotrope fate. Results We identified the transcription factors and epigenomic changes in chromatin that are associated with differentiation of POU1F1-expressing progenitors into thyrotropes using cell lines that represent an undifferentiated Pou1f1 lineage progenitor (GHF-T1) and a committed thyrotrope line that produces TSH (TαT1). We compared RNA-seq, ATAC-seq, histone modification (H3K27Ac, H3K4Me1, and H3K27Me3), and POU1F1 binding in these cell lines. POU1F1 binding sites are commonly associated with bZIP transcription factor consensus binding sites in GHF-T1 cells and Helix-Turn-Helix (HTH) or basic Helix-Loop-Helix (bHLH) factors in TαT1 cells, suggesting that these classes of transcription factors may recruit or cooperate with POU1F1 binding at unique sites. We validated enhancer function of novel elements we mapped near Cga, Pitx1, Gata2, and Tshb by transfection in TαT1 cells. Finally, we confirmed that an enhancer element near Tshb can drive expression in thyrotropes of transgenic mice, and we demonstrate that GATA2 enhances Tshb expression through this element. Conclusion These results extend the ENCODE multi-omic profiling approach to the pituitary gland, which should be valuable for understanding pituitary development and disease pathogenesis. Graphical abstract

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Promoter G-quadruplexes and transcription factors cooperate to shape the cell type-specific transcriptome

Nature Communications ◽

10.1038/s41467-021-24198-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Sara Lago ◽

Matteo Nadai ◽

Filippo M. Cernilogar ◽

Maryam Kazerani ◽

Helena Domíniguez Moreno ◽

...

Keyword(s):

Transcription Factors ◽

Binding Sites ◽

Specific Gene ◽

Open Chromatin ◽

Rna Seq ◽

Transcript Levels ◽

Promoter Sequences ◽

G Quadruplex ◽

Cell Type Specific ◽

Folding State

AbstractCell identity is maintained by activation of cell-specific gene programs, regulated by epigenetic marks, transcription factors and chromatin organization. DNA G-quadruplex (G4)-folded regions in cells were reported to be associated with either increased or decreased transcriptional activity. By G4-ChIP-seq/RNA-seq analysis on liposarcoma cells we confirmed that G4s in promoters are invariably associated with high transcription levels in open chromatin. Comparing G4 presence, location and transcript levels in liposarcoma cells to available data on keratinocytes, we showed that the same promoter sequences of the same genes in the two cell lines had different G4-folding state: high transcript levels consistently associated with G4-folding. Transcription factors AP-1 and SP1, whose binding sites were the most significantly represented in G4-folded sequences, coimmunoprecipitated with their G4-folded promoters. Thus, G4s and their associated transcription factors cooperate to determine cell-specific transcriptional programs, making G4s to strongly emerge as new epigenetic regulators of the transcription machinery.

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