scholarly journals Basic-Zipper-Type Transcription Factor FlbB Controls Asexual Development in Aspergillus nidulans

2007 ◽  
Vol 7 (1) ◽  
pp. 38-48 ◽  
Author(s):  
Oier Etxebeste ◽  
Min Ni ◽  
Aitor Garzia ◽  
Nak-Jung Kwon ◽  
Reinhard Fischer ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Nuclear Import ◽  
Cell Types ◽  
Regulatory Elements ◽  
Asexual Development ◽  
Quantitative Expression ◽  
Functional Relations ◽  
Asexual Spore ◽  
Hyphal Apex ◽  
Fungal Colony

ABSTRACT The fungal colony is a complex multicellular unit consisting of various cell types and functions. Asexual spore formation (conidiation) is integrated through sensory and regulatory elements into the general morphogenetic plan, in which the activation of the transcription factor BrlA is the first determining step. A number of early regulatory elements acting upstream of BrlA (fluG and flbA-E) have been identified, but their functional relations remain to be further investigated. In this report we describe FlbB as a putative basic-zipper-type transcription factor restricted to filamentous fungi. FlbB accumulates at the hyphal apex during early vegetative growth but is later found in apical nuclei, suggesting that an activating modification triggers nuclear import. Moreover, proper temporal and quantitative expression of FlbB is a prerequisite for brlA transcription, and misscheduled overexpression inhibits conidiation. We also present evidence that FlbB activation results in the production of a second diffusible signal, acting downstream from the FluG factor, to induce conidiation.

ATAC-STARR-seq v1

2021 ◽  
Author(s):  
Tyler Hansen ◽  
Emily Hodges
Keyword(s):  
Transcription Factor ◽  
Control Cell ◽  
Regulatory Region ◽  
Active Regions ◽  
Cell Types ◽  
Regulatory Elements ◽  
Transcription Factor Binding ◽  
Specific Gene ◽  
Factor Binding ◽  
Accessible Chromatin

Transcriptional enhancers control cell-type specific gene expression in humans and dysfunction can lead to debilitating diseases, including cancer. Identifying bona-fide enhancers is difficult due to a lack of spatial or sequence constraints. In addition, only a small percentage of the genome is accessible in matured cell types; and therefore, most enhancers are inactive due to their chromatin context rather than intrinsic properties of the DNA sequence itself. For this reason, we decided to assay regulatory activity exclusively within accessible chromatin. To do this, we combined assay for transposase-accessible chromatin using sequencing (ATAC-seq) with self-transcribing active regulatory region sequencing (STARR-seq); we call this method ATAC-STARR-seq. With ATAC-STARR-seq, we identify both active and silent regulatory elements in GM12878 B cells; these active and silent elements are enriched for transcription factor motifs and histone modifications associated with activating and repressing regulation, respectively. We also show that ATAC-STARR-seq quantifies chromatin accessibility and transcription factor binding. We integrate this information and subset active regions based on transcription factor binding profiles. Depending on the transcription factors bound, subsets are enriched for distinct reactome pathways. Altogether, this highlights the power of ATAC-STARR-seq to investigate the transcriptional regulatory landscape of the human genome.

scholarly journals Accurate promoter and enhancer identification in 127 ENCODE and Roadmap Epigenomics cell types and tissues by GenoSTAN

2016 ◽  
Author(s):  
Benedikt Zacher ◽  
Margaux Michel ◽  
Björn Schwalb ◽  
Patrick Cramer ◽  
Achim Tresch ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Genetic Variants ◽  
Hidden Markov ◽  
Data Distribution ◽  
Complex Trait ◽  
Cell Types ◽  
Regulatory Elements ◽  
Future Research ◽  
Dna Accessibility ◽  
Enhancer Identification

AbstractAccurate maps of promoters and enhancers are required for understanding transcriptional regulation. Promoters and enhancers are usually mapped by integration of chromatin assays charting histone modifications, DNA accessibility, and transcription factor binding. However, current algorithms are limited by unrealistic data distribution assumptions. Here we propose GenoSTAN (Genomic STate ANnotation), a hidden Markov model overcoming these limitations. We map promoters and enhancers for 127 cell types and tissues from the ENCODE and Roadmap Epigenomics projects, today’s largest compendium of chromatin assays. Extensive benchmarks demonstrate that GenoSTAN consistently identifies promoters and enhancers with significantly higher accuracy than previous methods. Moreover, GenoSTAN-derived promoters and enhancers showed significantly higher enrichment of complex trait-associated genetic variants than current annotations. Altogether, GenoSTAN provides an easy-to-use tool to define promoters and enhancers in any system, and our annotation of human transcriptional cis-regulatory elements constitutes a rich resource for future research in biology and medicine.

scholarly journals Ovarian Cancer Risk Variants are Enriched in Histotype-Specific Enhancers that Disrupt Transcription Factor Binding Sites

2020 ◽  
Author(s):  
Michelle R. Jones ◽  
Pei-Chen Peng ◽  
Simon G. Coetzee ◽  
Jonathan Tyrer ◽  
Alberto L. Reyes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Transcription Factor ◽  
Binding Sites ◽  
Transcription Factor Binding Sites ◽  
Cell Types ◽  
Regulatory Elements ◽  
P Value ◽  
Factor Binding ◽  
Risk Variants ◽  
Risk Snps

AbstractQuantifying the functional effects of complex disease risk variants can provide insights into mechanisms underlying disease biology. Genome wide association studies (GWAS) have identified 39 regions associated with risk of epithelial ovarian cancer (EOC). The vast majority of these variants lie in the non-coding genome, suggesting they mediate their function through the regulation of gene expression by their interaction with tissue specific regulatory elements (REs). In this study, by intersecting germline genetic risk data with regulatory landscapes of active chromatin in ovarian cancers and their precursor cell types, we first estimated the heritability explained by known common low penetrance risk alleles. The narrow sense heritability of both EOC overall and high grade serous ovarian cancer (HGSOCs) was estimated to be 5-6%. Partitioned SNP-heritability across broad functional categories indicated a significant contribution of regulatory elements to EOC heritability. We collated epigenomic profiling data for 77 cell and tissue types from public resources (Roadmap Epigenomics and ENCODE), and H3K27Ac ChIP-Seq data generated in 26 ovarian cancer-relevant cell types. We identified significant enrichment of risk SNPs in active REs marked by H3K27Ac in HGSOCs. To further investigate how risk SNPs in active REs influence predisposition to ovarian cancer, we used motifbreakR to predict the disruption of transcription factor binding sites. We identified 469 candidate causal risk variants in H3K27Ac peaks that break TF motifs (enrichment P-Value < 1×10−5 compared to control variants). The most frequently broken motif was REST (P-Value = 0.0028), which has been reported as both a tumor suppressor and an oncogene. These systematic functional annotations with epigenomic data highlight the specificity of the regulatory landscape and demonstrate functional annotation of germline risk variants is most informative when performed in highly relevant cell types.

scholarly journals Conservation of transcription factor binding specificities across 600 million years of bilateria evolution

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Kazuhiro R Nitta ◽  
Arttu Jolma ◽  
Yimeng Yin ◽  
Ekaterina Morgunova ◽  
Teemu Kivioja ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Specificity ◽  
Cell Types ◽  
Regulatory Elements ◽  
Relative Importance ◽  
Specific Expression ◽  
Differentiated Cells ◽  
In Cis ◽  
Human And Mouse

Divergent morphology of species has largely been ascribed to genetic differences in the tissue-specific expression of proteins, which could be achieved by divergence in cis-regulatory elements or by altering the binding specificity of transcription factors (TFs). The relative importance of the latter has been difficult to assess, as previous systematic analyses of TF binding specificity have been performed using different methods in different species. To address this, we determined the binding specificities of 242 Drosophila TFs, and compared them to human and mouse data. This analysis revealed that TF binding specificities are highly conserved between Drosophila and mammals, and that for orthologous TFs, the similarity extends even to the level of very subtle dinucleotide binding preferences. The few human TFs with divergent specificities function in cell types not found in fruit flies, suggesting that evolution of TF specificities contributes to emergence of novel types of differentiated cells.

Abstract 331: Genome-wide Analysis of Cardiac and Cardiac Fibroblasts Regulatory Elements Reveals Combinatorial Control of Gene Expression

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Tal Golan Lagziel ◽  
Lilac Caspi ◽  
Yair Lewis ◽  
Izhak Kehat
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Target Genes ◽  
Cardiac Fibroblasts ◽  
Cell Types ◽  
Regulatory Elements ◽  
Open Chromatin ◽  
Specific Expression ◽  
Control Of Gene Expression ◽  
Tissue Specific

The mammalian body contains several hundred cell types that share the same genome, but can express distinct gene signatures. This specification of gene expression is achieved through the activity of cis-regulatory genomic elements (CRE), such as enhancers, promoters, and silencers. The Assay for Transposase-Accessible Chromatin followed by sequencing (ATAC-seq) can identify nucleosome evicted open chromatin, an established marker of regulatory regions. Using a differential ATAC-seq approach, coupled with RNA-seq, H3K27ac ChiP-seq, and computational transcription factor (TFs) binding analysis we comprehensively mapped cell-type and condition specific cis regulatory elements for cardiac fibroblasts and cardiomyocytes, and outlined the TFs that control them. We show that in cardiomyocytes six main transcription factor groups, that control their own and each other’s expression, cooperatively bind discrete distal enhancers that are located at a variable distance from the transcription start site of their target genes. None of these factors is entirely tissue specific in expression, yet various combination of binding sites for these factors, densely clustered within a nucleosome length of genomic stretch make these CREs tissue specific. Multiple tissue specific CREs in turn, are clustered around highly tissue specific genes, and multiple factors, acting from the same and from different CREs can converge on these genes to control their tissue specific expression. Together our data puts forward a mechanistic multi-level combinatorial model for cardiac specific genes expression

scholarly journals Histone ChIP-Seq identifies differential enhancer usage during chondrogenesis as critical for defining cell-type specificity

2019 ◽  
Author(s):  
Kathleen Cheung ◽  
Matthew J. Barter ◽  
Julia Falk ◽  
Carole Proctor ◽  
Louise N. Reynard ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Transcription Factor ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Regulatory Elements ◽  
Luciferase Reporter ◽  
Epigenetic Mechanisms ◽  
Enhancer Activity ◽  
Chromatin States

AbstractEpigenetic mechanisms are known to regulate gene expression during chondrogenesis. In this study, we have characterised the epigenome during in vitro differentiation of human mesenchymal stem cells (hMSCs) into chondrocytes. Chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) was used to assess a range of N-terminal post-transcriptional modifications (marks) to histone H3 lysines (H3K4me3, H3K4me1, H3K27ac, H3K27me3 and H3K36me3) in both hMSCs and differentiated chondrocytes. Chromatin states were characterised using histone ChIP-seq and cis-regulatory elements were identified in chondrocytes. Chondrocyte enhancers were associated with chondrogenesis related gene ontology (GO) terms. In silico analysis and integration of DNA methylation data with chondrogenesis chromatin states revealed that enhancers marked by histone marks H3K4me1 and H3K27ac were de-methylated during in vitro chondrogenesis. Similarity analysis between hMSC and chondrocyte chromatin states defined in this study with epigenomes of cell-types defined by the Roadmap Epigenomics project revealed that enhancers are more distinct between cell-types compared to other chromatin states. Motif analysis revealed that the transcription factor SOX9 is enriched in chondrocyte enhancers. Luciferase reporter assays confirmed that chondrocyte enhancers characterised in this study exhibited enhancer activity which may be modulated by inducing DNA methylation and SOX9 overexpression. Altogether, these integrated data illustrate the cross-talk between different epigenetic mechanisms during chondrocyte differentiation.SummaryHuman mesenchymal stem cells are able to differentiate into chondrocytes, the cell type found in cartilage, making them an accessible system to study gene regulation during this process. Epigenetic mechanisms such as histone modifications and DNA methylation together with transcription factor binding play a role in activating and repressing gene expression. In this study, we investigated the genome-wide histone modification changes during chondrocyte differentiation. Integration of this data with DNA methylation and SOX9 transcription factor ChIP-seq revealed epigenetic changes at gene enhancer elements. Regions of the genome that transition from non-enhancers to enhancers in chondrocytes are enriched for SOX9 transcription factor binding sites. Luciferase reporter assays revealed that enhancer activity may be modulated by manipulating DNA methylation and SOX9 expression. This study has defined important regulatory elements in chondrocytes which could serve as targets for future mechanistic studies.

scholarly journals Glucocorticoid receptor wields chromatin interactions to tune transcription for cytoskeleton stabilization in podocytes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hong Wang ◽  
Aiping Duan ◽  
Jing Zhang ◽  
Qi Wang ◽  
Yuexian Xing ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Glucocorticoid Receptor ◽  
Protective Effect ◽  
Histone Modification ◽  
Regulatory Networks ◽  
Target Gene ◽  
Regulatory Elements ◽  
Chromatin Interactions ◽  
Super Enhancer

AbstractElucidating transcription mediated by the glucocorticoid receptor (GR) is crucial for understanding the role of glucocorticoids (GCs) in the treatment of diseases. Podocyte is a useful model for studying GR regulation because GCs are the primary medication for podocytopathy. In this study, we integrated data from transcriptome, transcription factor binding, histone modification, and genome topology. Our data reveals that the GR binds and activates selective regulatory elements in podocyte. The 3D interactome captured by HiChIP facilitates the identification of remote targets of GR. We found that GR in podocyte is enriched at transcriptional interaction hubs and super-enhancers. We further demonstrate that the target gene of the top GR-associated super-enhancer is indispensable to the effective functioning of GC in podocyte. Our findings provided insights into the mechanisms underlying the protective effect of GCs on podocyte, and demonstrate the importance of considering transcriptional interactions in order to fine-map regulatory networks of GR.

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