Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA311179 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3151870.fastq.gz | Fastqsanger.gz | |||
| SRR3151880.fastq.gz | Fastqsanger.gz | |||
| SRR3151861.fastq.gz | Fastqsanger.gz | |||
| SRR3151871.fastq.gz | Fastqsanger.gz | |||
| SRR3151881.fastq.gz | Fastqsanger.gz |
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Project description:Pioneer transcription factor FoxA maintains an open nucleosome configuration for tissue-specific gene activation [MNase-Seq]
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Project description:Nuclear DNA is wrapped around core histones to form nucleosomes, which constrains how transcription factors bind to gene regulatory sequences. Pioneer transcription factors have the special ability to bind target DNA on nucleosomes and initiate gene regulatory events, often leading to a local opening of chromatin. Yet the nucleosomal configuration of such open chromatin and the basis for chromatin opening is unclear. Here we combine low and high levels of MNase digestion along with core histone ChIP-seq to assess the presence of nucleosomes at enhancers and promoters in mouse liver. We find that the pioneer factor FoxA displaces linker histone H1, thereby keeping enhancer nucleosomes accessible in chromatin and helping other transcription factors bind. MNase-accessible nucleosomes, bound by transcription factors, are retained substantially more at liver-specific enhancers than promoters and tissue-ubiquitous enhancers. Thus, nucleosomes are not exclusively repressive to gene regulation when they are retained with, and exposed by, pioneer factors.
2016-04-08 | GSE77670 | GEO
Project description:Tissue-specific DNA methylation patterns are created by transcription factors that recruit methylation and demethylation enzymes to cis-regulatory elements. To date, it is not known whether transcription factors are needed to continuously maintain methylation profiles in development and mature tissues or whether they only establish these marks during organ development. We queried the role of the pioneer factor FoxA in generating hypomethylated DNA at liver enhancers. We discovered a set of FoxA binding sites that undergo regional, FoxA-dependent demethylation during organ development. Conditional ablation of FoxA genes in the adult liver demonstrated that continued FoxA presence was not required to maintain the hypomethylated state, even when massive cell proliferation was induced. This study provides strong evidence for the stable, epigenetic nature of tissue-specific DNA methylation patterns directed by lineage-determining transcription factors during organ development.
2021-04-20 | GSE124384 | GEO
Project description:FOXA pioneer transcription factors (TFs) associate with primed enhancers in endodermal organ precursors. Using a human stem cell model of pancreas differentiation, we here discover that only a subset of pancreatic enhancers is FOXA-primed, whereas the majority is unprimed and engages FOXA upon lineage induction. Primed enhancers are enriched for signal-dependent TF motifs and harbor abundant and strong FOXA motifs. Unprimed enhancers harbor fewer, more degenerate FOXA motifs, and FOXA recruitment to unprimed but not primed enhancers requires pancreatic TFs. Strengthening FOXA motifs at an unprimed enhancer near NKX6.1 renders FOXA recruitment pancreatic TF-independent, induces priming, and broadens the NKX6.1 expression domain. We make analogous observations about FOXA binding during hepatic and lung development. Our findings suggest a dual role for FOXA in endodermal organ development: First, FOXA facilitate signal-dependent lineage initiation via enhancer priming, and second, FOXA enforce organ cell type-specific gene expression via indirect recruitment by lineage-specific TFs.
2021-10-18 | GSE148368 | GEO
Project description:In higher eukaryotes, enhancers and promoters share many properties, including binding of transcription factors, existing in open chromatin, and bidirectional transcription. Yet the structural features that distinguish enhancers and promoters are unclear. Genome-wide micrococcal nuclease (MNase) studies previously interpreted MNase hypersensitivity to indicate that active enhancers and promoters are nucleosome-free, yet other studies found histone variants and post-translational modifications at active enhancers. We find that prior MNase genomic studies have an overdigestion bias and that low-level MNase digestion, coupled with mapping core histones, reveals two classes of MNase-hypersensitive sites: at active promoters, which are nucleosome depleted, and at tissue-specific enhancers, which retain core histones and co-bound transcription factors substantially more than promoters. Hypersensitivity of active enhancer nucleosomes may reflect their preferential exposure in chromatin and can be maintained by pioneer transcription factors such as FoxA. These findings unveil fundamental differences in the chromatin structure of active enhancers and promoters.
2016-04-08 | GSE57557 | GEO
Project description:In higher eukaryotes, enhancers and promoters share many properties, including binding of transcription factors, existing in open chromatin, and bidirectional transcription. Yet the structural features that distinguish enhancers and promoters are unclear. Genome-wide micrococcal nuclease (MNase) studies previously interpreted MNase hypersensitivity to indicate that active enhancers and promoters are nucleosome-free, yet other studies found histone variants and post-translational modifications at active enhancers. We find that prior MNase genomic studies have an overdigestion bias and that low-level MNase digestion, coupled with mapping core histones, reveals two classes of MNase-hypersensitive sites: at active promoters, which are nucleosome depleted, and at tissue-specific enhancers, which retain core histones and co-bound transcription factors substantially more than promoters. Hypersensitivity of active enhancer nucleosomes may reflect their preferential exposure in chromatin and can be maintained by pioneer transcription factors such as FoxA. These findings unveil fundamental differences in the chromatin structure of active enhancers and promoters.
2016-04-08 | GSE57556 | GEO
Project description:In higher eukaryotes, enhancers and promoters share many properties, including binding of transcription factors, existing in open chromatin, and bidirectional transcription. Yet the structural features that distinguish enhancers and promoters are unclear. Genome-wide micrococcal nuclease (MNase) studies previously interpreted MNase hypersensitivity to indicate that active enhancers and promoters are nucleosome-free, yet other studies found histone variants and post-translational modifications at active enhancers. We find that prior MNase genomic studies have an overdigestion bias and that low-level MNase digestion, coupled with mapping core histones, reveals two classes of MNase-hypersensitive sites: at active promoters, which are nucleosome depleted, and at tissue-specific enhancers, which retain core histones and co-bound transcription factors substantially more than promoters. Hypersensitivity of active enhancer nucleosomes may reflect their preferential exposure in chromatin and can be maintained by pioneer transcription factors such as FoxA. These findings unveil fundamental differences in the chromatin structure of active enhancers and promoters.
2016-04-08 | GSE57558 | GEO
Project description:The FoxA family of pioneer transcription factors regulate hepatitis B virus (HBV) transcription, and hence viral replication. Hepatocyte-specific FoxA-deficiency in the HBV transgenic mouse model of chronic infection prevents the transcription of the viral DNA genome as a result of the failure of the developmentally controlled conversion of 5-methylcytosine residues to cytosine during postnatal hepatic maturation. These observations suggest that pioneer transcription factors such as FoxA, which mark genes for expression at subsequent developmental steps in the cellular differentiation program, mediate their effects by reversing the DNA methylation status of their target genes to permit their ensuing expression when the appropriate tissue-specific transcription factor combinations arise during development. Furthermore, as the FoxA-deficient HBV transgenic mice are viable, the specific developmental timing, abundance and isoform type of pioneer factor expression must permit all essential liver gene expression to occur at a level sufficient to support adequate liver function. This implies that pioneer transcription factors can recognize and mark their target genes in distinct developmental manners dependent upon, at least in part, the concentration and affinity of FoxA for its binding sites within enhancer and promoter regulatory sequence elements. This selective marking of cellular genes for expression by the FoxA pioneer factor compared to HBV may offer the opportunity for the specific silencing of HBV gene expression and hence the resolution of chronic HBV infections which annually are responsible for approximately one million deaths worldwide due to liver cirrhosis and hepatocellular carcinoma.
2017-02-16 | GSE89832 | GEO
Project description:While enhancers are often regulated at the level of accessibility by pioneer factors, promoters tend to be constitutively accessible and poised for activation by paused Pol II — thus are often not considered as sites of developmental regulation. Here we show that the accessibility of promoters and the acquisition of paused Pol II can also be subject to developmental regulation by pioneer factors. We show that Lola-I, a Drosophila zinc finger transcription factor, is ubiquitously expressed at the end of embryogenesis and causes its target promoters to become accessible and acquire paused Pol II throughout the embryo. This promoter transition is required but not sufficient for tissue-specific target gene expression. Lola-I mediates this function by binding to the edges of the promoter nucleosomes, which leads to their depletion, similar to the action of pioneer factors at enhancers. These results uncover a level of regulation for promoters that is normally found at enhancers, providing further evidence that promoters and enhancers display unexpectedly similar characteristics.
2023-06-23 | GSE200869 | GEO
Project description:While enhancers are often regulated at the level of accessibility by pioneer factors, promoters tend to be constitutively accessible and poised for activation by paused Pol II — thus are often not considered as sites of developmental regulation. Here we show that the accessibility of promoters and the acquisition of paused Pol II can also be subject to developmental regulation by pioneer factors. We show that Lola-I, a Drosophila zinc finger transcription factor, is ubiquitously expressed at the end of embryogenesis and causes its target promoters to become accessible and acquire paused Pol II throughout the embryo. This promoter transition is required but not sufficient for tissue-specific target gene expression. Lola-I mediates this function by binding to the edges of the promoter nucleosomes, which leads to their depletion, similar to the action of pioneer factors at enhancers. These results uncover a level of regulation for promoters that is normally found at enhancers, providing further evidence that promoters and enhancers display unexpectedly similar characteristics.
2023-06-23 | GSE200870 | GEO