Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1305492 | ENA |
REPOSITORIES: ENA
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Project description:Transcription factors can promote gene expression through activation domains. Whole-genome screens have systematically mapped activation domains in transcription factors, but not in non-transcription factor proteins (e.g., chromatin regulators, coactivators). To fill this knowledge gap, we employed the activation domain predictor PADDLE to analyze the proteomes of Arabidopsis thaliana and Saccharomyces cerevisiae. We screened 18,000 predicted activation domains from >800 non-transcription factor genes in both species, confirming that 89% of candidate proteins contain active fragments. Our work enables the annotation of hundreds of nuclear proteins as putative coactivators, many of which have never been ascribed any function in plants. Analysis of peptide sequence compositions reveals how the distribution of key amino acids dictates activity. Finally, we validated short, 'universal' activation domains with comparable performance to state-of-the-art activation domains used for genome engineering. Our approach enables the genome-wide discovery and annotation of activation domains that can function across diverse eukaryotes.
2024-04-24 | GSE247147 | GEO
Project description:Transcription factor binding to enhancer and promoter regions is critical for gene activation. To understand how cell-specific gene expression patterns are generated, we studied the developmental timing of association of two prominent hepatic transcription factors with gene regulatory regions. We found that most individual binding events displayed extraordinarily high temporal variations during liver development. Early and persistent binding is necessary but not sufficient for gene activation. Stable gene expression patterns are mainly generated by the combinatorial activity of multiple transcription factors, which mark regulatory regions long before activation and promote progressive broadening of active chromatin domains. Both, temporally stable and dynamic binding events contribute to the developmental maturation of active promoter configurations. The results reveal a developmental “bookmarking” function of transcription factors, and illuminate remarkable parallels between the principles employed for gene activation during development, evolution and upon mitotic exit.
2020-02-18 | GSE137066 | GEO
Project description:Transcription factors mediate precise regulation of gene expression programs to modulate key biological processes. In addition to controlling HIV transcription, Tat appears to modulate cellular transcription to alter the biology of target immune cells and generate a permissive state for HIV infection. However, the molecular mechanisms of transcriptional control have remained elusive. Here, we identified the direct target genes of Tat using genomics and defined mechanisms by which Tat selectively rewires cellular transcriptional programs. Interestingly, Tat functions as both transcriptional activator and repressor of a defined set of genes sharing functional annotations and regulated by master transcriptional regulators such as T-cell identity factors. Tat is recruited to precise genomic domains (promoters and intragenic enhancers) through interaction with master transcriptional regulators to control both the transcription initiation and elongation steps. Tat mediates transcription initiation by modulating Pol II recruitment to promoters and intragenic enhancers and fine-tuning chromatin looping. Tat stimulates or blocks RNA Polymerase (Pol) II recruitment or promoter-proximal pause release thereby promoting gene activation or repression, respectively. Global analysis of chromatin signatures revealed correlation of transcription activity marks with Pol II recruitment or pause release status at gene promoters and enhancers, and transcription elongation at coding units. We propose that Tat has evolved these unique properties to hijack precise genomic domains to control cellular transcription using unexpected regulatory mechanisms, which showed marked differences to the regulation of the HIV genome. Our studies also reveal that Tat can be used as a molecular probe to decode general principles of transcriptional regulation. ChIP of various DNA binding proteins
2015-06-15 | E-GEOD-65687 | biostudies-arrayexpress
Project description:Transcription factors activate genes through the phase separation capacity of their activation domains
| PRJNA493113 | ENA
Project description:Understanding how chromatin organisation is duplicated on the two daughter strands is a central question in epigenetics. In mammals, following the passage of the replisome, nucleosomes lose their defined positioning and transcription contributes to their re-organisation. However, whether transcription plays a greater role in the organization of chromatin following DNA replication remains unclear. Here we have monitored protein re-association to newly replicated DNA upon inhibition of transcription using iPOND coupled to quantitative mass spectrometry. We show that RNAPII acts to promote the re-association of hundreds of proteins with newly replicated chromatin, including ATP-dependent remodellers, transcription factors, DNA repair factors, and histone methyltransferases.
2024-02-14 | PXD046514 | Pride
Project description:Mutations in PHF8 are associated with X-linked mental retardationand cleft lip/cleft palate. PHF8 contains a plant homeodomain(PHD) in its N-terminus and is member of a family of JmjC-domaincontaining proteins. While PHDs can act as methyl lysine recognitionmotifs, JmjC-domains can catalyze lysine demethylation. Here,we show that PHF8 is a histone demethylase that removes repressivehistone H3 dimethyl lysine 9 marks. Our biochemical analysisrevealed specific association of the PHF8 PHD domain with histoneH3 trimethylated at lysine 4 (H3K4me3). Chromatin-immunoprecipitationfollowed by high throughput sequencing indicated that PHF8 isenriched at transcription start sites of many active or poisedgenes, mirroring the presence of RNA polymerase II (RNAPII)and of H3K4me3-bearing nucleosomes. We show that PHF8 can actas a transcriptional co-activator and its activation functionlargely depends on binding of the PHD to H3K4me3. Furthermore,we present evidence for direct interaction of PHF8 with theC-terminal domain of RNAPII. Importantly, a PHF8 disease mutantis defective in demethylation and in co-activation. This isthe first demonstration of a chromatin-modifying enzyme whichis globally recruited to promoters through its association withH3K4me3 and RNAPII. This SuperSeries is composed of the following subset Series: GSE20563: Knockdown of PHF8 in HeLa S3 cells GSE20725: ChIP-Seq of PHF8 and H3K4me3 Refer to individual Series
2010-04-26 | E-GEOD-20753 | biostudies-arrayexpress
Project description:This study was designed to investigate DNA supercoiling across the human genome and to understand how supercoiling domains impact on higher levels of genome organisation. DNA supercoiling is an inherent consequence of twisting DNA and is critical for regulating gene expression and DNA replication. However, DNA supercoiling at a genomic scale in human cells is uncharacterized. To map supercoiling we used biotinylated-trimethylpsoralen as a DNA structure probe to show the genome is organized into supercoiling domains. Domains are formed and remodeled by RNA polymerase and topoisomerase activities and are flanked by GC-AT boundaries and CTCF binding sites. Under-wound domains are transcriptionally active, enriched in topoisomerase I, M-bM-^@M-^\openM-bM-^@M-^] chromatin fibers and DNaseI sites, but are depleted of topoisomerase II. Furthermore DNA supercoiling impacts on additional levels of chromatin compaction as under-wound domains are cytologically decondensed, topologically constrained, and decompacted by transcription of short RNAs. We suggest that supercoiling domains create a topological environment that facilitates gene activation providing an evolutionary purpose for clustering genes along chromosomes. The gene transcription of 3 independent biological replicates were investigated
2013-02-17 | E-GEOD-43449 | biostudies-arrayexpress
Project description:Proinflammatory stimuli rapidly and globally remodel chromatin landscape, thereby enabling transcriptional responses. Yet, the mechanisms coupling chromatin regulators to the master regulatory inflammatory transcription factor NF-kB remain poorly understood. We report in human endothelial cells (ECs) that activated NF-kB binds to enhancers, provoking a rapid, global redistribution of BRD4 preferentially at super-enhancers, large enhancer domains highly bound by chromatin regulators. Newly established NF-kB super-enhancers drive nearby canonical inflammatory response genes. In both ECs and macrophages BET bromodomain inhibition prevents super-enhancer formation downstream of NF-kB activation, abrogating proinflammatory transcription. In TNFa-activated endothelium this culminates in functional suppression of leukocyte rolling, adhesion and transmigration. Sustained BET bromodomain inhibitor treatment of LDLr -/- animals suppresses atherogenesis, a disease process rooted in pathological vascular inflammation involving endothelium and macrophages. These data establish BET-bromodomains as key effectors of inflammatory response through their role in the dynamic, global reorganization of super-enhancers during NF-kB activation. ChIP-Seq for various transcription factors, RNA Polymerase II, and histone modifications in human endothelial cells
2014-09-29 | E-GEOD-53998 | biostudies-arrayexpress
Project description:Polycomb group (PcG) proteins initiate the formation of repressed chromatin domains and regulate developmental gene expression. A mammalian PcG protein, Enhancer of Zeste homolog 2 (Ezh2), triggers transcriptional repression by catalyzing the addition of methyl groups onto lysine-27 of histone H3 (H3K27me2/3)1. This action facilitates the binding of other PcG proteins to histone H3 and compaction of chromatin. Interestingly, there exists a paralog of Ezh2, termed Ezh1, whose primary function remains unclear. Here, we provide evidence for genome-wide association of Ezh1 with active epigenetic marks, RNA polymerase II (PolII) and mRNA production. Ezh1 depletion reduced global PolII occupancy within gene bodies and resulted in delayed transcriptional activation during differentiation of skeletal muscle cells. Conversely, ectopic expression of wild-type Ezh1 led to premature gene activation and rescued PolII-elongation defects in Ezh1-depleted cells. Collectively, these findings reveal an unanticipated role of a PcG protein in promoting mRNA transcription. Examination of 3 different histone modifications, 3 modified forms of RNA polymerase II, Ezh1, Ezh2 and mRNA levels in a skeletal muscle cells at various developmental stages.
2011-11-23 | E-GEOD-25549 | biostudies-arrayexpress
Project description:San1 is an E3 ubiquitin ligase involved in nuclear protein quality control via its interaction with intrinsically disordered proteins for ubiquitylation and 26S proteasomal degradation. Since a number of transcription/chromatin regulatory factors contain intrinsically disordered domains and can be inhibitory to transcription when in excess, San1 might be involved in regulation of transcription. To address this, we carried out ChIP-seq (Chromatin immunoprecipitation sequencing) here to analyze the role of San1 in genome-wide association of TBP (TATA-box binding protein that nucleates the preinitiation complex formation at the promoter for transcription initiation) and RNA polymerase II (that is recruited to the promoter by TBP and subsequently engaged in transcription elongation at the coding sequence for mRNA biosynthesis). Our results reveal the genome-wide role of San1 in facilitating the recruitment of TBP to the promoter, thus indicating its involvement in promoting the preinitiation complex formation for transcription initiation. Further, we find the global role of San1 in regulating RNA polymerase II at the coding sequence.
2021-12-04 | GSE190065 | GEO