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Mus musculus

ABSTRACT: SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers [next-generation sequencing]

PROVIDER: PRJNA288531 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR2082690.fastq.gz	Fastqsanger.gz
	SRR2082700.fastq.gz	Fastqsanger.gz
	SRR2082710.fastq.gz	Fastqsanger.gz
	SRR2082691.fastq.gz	Fastqsanger.gz
	SRR2082701.fastq.gz	Fastqsanger.gz

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SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers

Project description:SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers

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Mus musculus

Project description:SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers [array]

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Epigenetic landscapes in wild-type and dimer-mutant Notch regulated T-LL cells

Project description:NOTCH/RBPJ/MAML ternary transcriptional complex binds to regulatory element and drives gene expression. The complex can function as monomer and dimer. How dimeric complexes regulate gene expression in human cancer is not well studied. Here, we integrate genomic data sets and analyze Notch dimeric complexes-regulated transcriptome and cis-regulatory elements. A subset of coding and non-coding RNA is Notch dimeric complexes-associated. Dimeric complexes recognition sequence enriched in functional dynamic Notch sites and majority of dimer recognition sequence located in (super-)enhancers. Using CRISPR-Cas9-mediated genome editing, we evaluated the function of one dimer-responsive element located in the promoter region of a noncoding RNA NDANR1 and 5' end 16kb away from HES5. Mutation of SPS in this element reduced expression of HES5 and NDANR1. This finding indicates that dimer-responsive elements can function as enhancer for HES5 and at the same time can function as promoter for noncoding RNA NDANR1. Our study reveals the pervasive role of Notch dimeric complexes in transcriptional regulation in human cancer genome.

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SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers [next-generation sequencing]

Project description:Development of an alternative method to ChIP for the identification of DNA bound by transcriptional complexes assayed using next-generation sequencing Next-generation sequencing data from sites identified by different Notch complexes using SpDamID-seq and compared against FAIRE and ChIP data

2015-08-01 | E-GEOD-70387 | biostudies-arrayexpress

Sequence dependency and regulatory function of dimeric NOTCH1/RBPJ complexes on coding and non-coding transcription in T-lymphoblastic leukemia

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Project description:Chromatin immunoprecipitation of Klf4 in NMuMG cells identifies gene promoter sequences that are directly bound by Klf4. Chromatin immunoprecipitation using a Klf4-specific antibody in NMuMG cells followed by next generation sequencing (ChIP-Seq).

2013-08-01 | E-GEOD-49445 | biostudies-arrayexpress

SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers [next-generation sequencing]

Project description:Development of an alternative method to ChIP for the identification of DNA bound by transcriptional complexes assayed using next-generation sequencing

2015-08-01 | GSE70387 | GEO

SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers [array]

Project description:Development of an alternative method to ChIP for the identification of DNA bound by transcriptional complexes assayed using Nimblegen arrays Nimblegen promoter arrays allowing identification of sites bound by different Notch complexes using SpDamID

2015-08-01 | E-GEOD-70388 | biostudies-arrayexpress

An improved SELEX-Seq strategy for characterizing DNA-binding specificity of transcription factor: NF-M-NM-:B as an example

Project description:We provided an improved SELEX-Seq strategy for characterizing DNA-binding specificity of transcription factor. We valided the strategy by characterzing the DNA-binding specificty of NF-M-NM-:B p50 dimer. Proteins of the Nf-kappab family were bound to DNA oligonucleotides containing a degenerate region. The protein-DNA complexes were selected after one or multiple rounds of SELEX and the DNA molecules were deep sequenced.

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NOTCH1/RBPJ complexes drive target gene expression through dynamic interactions with super-enhancers

Project description:The main oncogenic driver in T-lymphoblastic leukemia (T-LL) is NOTCH1, which activates genes by forming chromatin-associated Notch transcription complexes. Gamma-secretase (GSI) inhibitor treatment prevents NOTCH1 nuclear localization, but most genes with NOTCH1 binding sites are insensitive to GSI. Here, we demonstrate that fewer than 10% of NOTCH1 binding sites show dynamic changes in NOTCH1 occupancy when T-LL cells are toggled between the Notch-on and –off states with GSI. Dynamic NOTCH1 sites are functional, being highly associated with Notch target genes, are located mainly in distal enhancers, and frequently overlap with RUNX1 binding. In line with the latter association, we show that expression of IL7R, a gene with key roles in normal T cell development and in T-LL, is coordinately regulated by Runx factors and dynamic NOTCH1 binding to distal enhancers. Like IL7R, most Notch target genes and associated dynamic NOTCH1 binding sites co-occupy chromatin domains defined by constitutive binding of CCCTC binding factor (CTCF), which appears to restrict the regulatory potential of dynamic NOTCH1 sites. More remarkably, the majority of dynamic NOTCH1 sites lie in super-enhancers, distal elements with exceptionally broad and high levels of H3K27ac. Changes in Notch occupancy produces dynamic alterations in H3K27ac levels across the entire breadth of super-enhancers and in the promoters of nearby Notch target genes. These findings link regulation of super-enhancer function to NOTCH1, a master regulatory factor and potent oncoprotein in the context of immature T cells, and delineate a generally applicable roadmap for identifying functional Notch sites in cellular genomes. NOTCH1/RBPJ complexes binding dynamics in human T-LL

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