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Changes in chromatin accessibility and gene expression induced by overexpression of ONECUT transcription factors

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Rattus norvegicus Homo sapiens

PROVIDER: GSE120131 | GEO | 2019/04/05

REPOSITORIES: GEO

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ONECUT transcription factors induce neuronal characteristics and remodel chromatin accessibility.

Project description:Remodeling of chromatin accessibility is necessary for successful reprogramming of fibroblasts to neurons. However, it is still not fully known which transcription factors can induce a neuronal chromatin accessibility profile when overexpressed in fibroblasts. To identify such transcription factors, we used ATAC-sequencing to generate differential chromatin accessibility profiles between human fibroblasts and iNeurons, an in vitro neuronal model system obtained by overexpression of Neurog2 in induced pluripotent stem cells (iPSCs). We found that the ONECUT transcription factor sequence motif was strongly associated with differential chromatin accessibility between iNeurons and fibroblasts. All three ONECUT transcription factors associated with this motif (ONECUT1, ONECUT2 and ONECUT3) induced a neuron-like morphology and expression of neuronal genes within two days of overexpression in fibroblasts. We observed widespread remodeling of chromatin accessibility; in particular, we found that chromatin regions that contain the ONECUT motif were in- or lowly accessible in fibroblasts and became accessible after the overexpression of ONECUT1, ONECUT2 or ONECUT3. There was substantial overlap with iNeurons, still, many regions that gained accessibility following ONECUT overexpression were not accessible in iNeurons. Our study highlights both the potential and challenges of ONECUT-based direct neuronal reprogramming.

| S-EPMC6582315 | biostudies-literature

Changes in chromatin accessibility and gene expression induced by overexpression of ONECUT transcription factors

Project description:Changes in chromatin accessibility and gene expression induced by overexpression of ONECUT transcription factors

| PRJNA491706 | ENA

Dynamics of chromatin accessibility and gene regulation by MADS-domain transcription factors in flower development

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-02-03 | E-GEOD-46987 | biostudies-arrayexpress

Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type-specific master transcription factors

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-08-14 | E-GEOD-56840 | biostudies-arrayexpress

Dynamic regulation of chromatin accessibility by pluripotency transcription factors across the cell cycle

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-11-26 | GSE134680 | GEO

NFI Transcription Factors Govern Stem Cell Chromatin Accessibility and Guard Against Irreversible Hair Loss

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-04-01 | GSE135146 | GEO

Global changes in chromatin accessibility and transcription in growth hormone-secreting pituitary adenoma.

Project description:PurposeGrowth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of growth hormone and insulin-like growth factor 1, causing increased morbidity and mortality. Previous studies have investigated the transcription of GHPA. However, the gene regulatory landscape has not been fully characterized. The objective of our study was to unravel the changes in chromatin accessibility and transcription in GHPA.MethodsSix patients diagnosed with GHPA in the Department of Neurosurgery at Huashan Hospital were enrolled in our study. Primary pituitary adenoma tissues and adjacent normal pituitary specimens with no morphologic abnormalities from these six patients were obtained at surgery. RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were applied to investigate the underlying relationship between gene expression and chromatin accessibility changes in GHPA.ResultsTotally, 1528 differential expression genes (DEGs) were identified by transcriptomics analyses, including 725 up-regulated and 803 down-regulated. Further, we obtained 64 significantly DEGs including 10 DEGs were elevated and 54 DEGs were negligibly expressed in tumors tissues. The up-regulated DEGs were mainly involved in terms related to synapse formation, nervous system development and secretory pathway. In parallel, 3916 increased and 2895 decreased chromatin-accessible regions were mapped by ATAC-seq. Additionally, the chromatin accessible changes were frequently located adjacent to transcription factor CTCF and Rfx2 binding site.ConclusionsOur results are the first to demonstrate the landscape of chromatin accessibility in GHPA, which may contribute to illustrate the underlying transcriptional regulation mechanism of this disease.

| S-EPMC9584994 | biostudies-literature

Dynamic regulation of chromatin accessibility by pluripotency transcription factors across the cell cycle.

Project description:The pioneer activity of transcription factors allows for opening of inaccessible regulatory elements and has been extensively studied in the context of cellular differentiation and reprogramming. In contrast, the function of pioneer activity in self-renewing cell divisions and across the cell cycle is poorly understood. Here we assessed the interplay between OCT4 and SOX2 in controlling chromatin accessibility of mouse embryonic stem cells. We found that OCT4 and SOX2 operate in a largely independent manner even at co-occupied sites, and that their cooperative binding is mostly mediated indirectly through regulation of chromatin accessibility. Controlled protein degradation strategies revealed that the uninterrupted presence of OCT4 is required for post-mitotic re-establishment and interphase maintenance of chromatin accessibility, and that highly OCT4-bound enhancers are particularly vulnerable to transient loss of OCT4 expression. Our study sheds light on the constant pioneer activity required to maintain the dynamic pluripotency regulatory landscape in an accessible state.

| S-EPMC6890464 | biostudies-literature

Dynamics of chromatin accessibility and gene regulation by MADS-domain transcription factors in flower development

Project description:This SuperSeries is composed of the SubSeries listed below.

2014-02-03 | GSE46987 | GEO

Drug-induced chromatin accessibility changes associate with sensitivity to liver tumor promotion.

Project description:Liver cancer susceptibility varies amongst humans and between experimental animal models because of multiple genetic and epigenetic factors. The molecular characterization of such susceptibilities has the potential to enhance cancer risk assessment of xenobiotic exposures and disease prevention strategies. Here, using DNase I hypersensitivity mapping coupled with transcriptomic profiling, we investigate perturbations in cis-acting gene regulatory elements associated with the early stages of phenobarbital (PB)-mediated liver tumor promotion in susceptible versus resistant mouse strains (B6C3F1 versus C57BL/6J). Integrated computational analyses of strain-selective changes in liver chromatin accessibility underlying PB response reveal differential epigenetic regulation of molecular pathways associated with PB-mediated tumor promotion, including Wnt/β-catenin signaling. Complementary transcription factor motif analyses reveal mouse strain-selective gene regulatory networks and a novel role for Stat, Smad, and Fox transcription factors in the early stages of PB-mediated tumor promotion. Mapping perturbations in cis-acting gene regulatory elements provides novel insights into the molecular basis for susceptibility to xenobiotic-induced rodent liver tumor promotion and has the potential to enhance mechanism-based cancer risk assessments of xenobiotic exposures.

| S-EPMC6795216 | biostudies-literature

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