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MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation

ABSTRACT: MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation

PROVIDER: PRJNA472068 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7184280_1.fastq.gz	Fastqsanger.gz
	SRR7184280_2.fastq.gz	Fastqsanger.gz
	SRR7184290_1.fastq.gz	Fastqsanger.gz
	SRR7184290_2.fastq.gz	Fastqsanger.gz
	SRR7184281_1.fastq.gz	Fastqsanger.gz

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MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation

Project description:Evidence of widespread transcription at active enhancers became apparent. However, our understanding about the functions of enhancer RNAs (eRNAs) and their mechanistic roles remains incomplete. Here, we study eRNA regulation and function using skeletal myoblast differentiation as a paradigm. We provide a panoramic view of enhancer transcription and uncover reprogramming in enhancer transcription occurring during myogenic differentiation. We demonstrate the critical role of MyoD in activating eRNAs production. Results from in depth dissection of two eRNAs transcribed from super enhancers (seRNA-1 and -2) suggest that seRNAs can promote myogenic differentiation in vitro and in vivo; the induction of the seRNAs is in coordination with the activation of the neighboring genes and seRNA loss largely impairs their expression. Mechanistically, we elucidate these seRNAs specifically bind to heterogeneous nuclear ribonucleoprotein L (hnRNPL) and modulate hnRNPL binding to the target promoter. A CAAA tract on the seRNA was identified to be essential in mediating the interaction between seRNA-1 and hnRNPL. Disruption of seRNA-hnRNPL interaction attenuates Pol II and H3K36me3 deposition at the target genes, in coincidence with the reduction of their expression. Furthermore, analyses of hnRNPL binding transcriptome-wide reveals its association with eRNAs is a general phenomenon in multiple cells. Collectively, we propose that eRNA-hnRNPL interaction contributes to target mRNA activation.

2019-10-03 | GSE114659 | GEO

MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [CLIP-Seq]

2019-10-03 | GSE114656 | GEO

MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [RNA-Seq]

2019-10-03 | GSE114658 | GEO

MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [GRO-Seq]

2019-10-03 | GSE114657 | GEO

MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [RNA-Seq]

Project description:MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [RNA-Seq]

| PRJNA472071 | ENA

MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [GRO-Seq]

Project description:MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [GRO-Seq]

| PRJNA472072 | ENA

MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [CLIP-Seq]

Project description:MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [CLIP-Seq]

| PRJNA472070 | ENA

Motif Variation Regulates the Affinity Landscape and Epigenetic State of the MyoD Cistrome

Project description:The cis-regulatory code is the cellular lexicon by which the transcriptional machinery converts sequence information within cis-regulatory modules (CRMs) into gene expression output. Tissue-specific transcription factors such as MyoD orchestrate gene expression programs by binding to short DNA motifs called E-boxes within their target CRMs to modulate chromatin state and to fine-tune gene expression output. Despite extensive research, how the relatively short and ubiquitously distributed E-box motifs contribute to binding specificity, assembly and the functional output of the transcriptional machinery remains poorly understood. Here, we have carried out an integrative analysis of the relationship between MyoD occupancy, nucleosome positioning, CRMs-associated histone marks and motif sequences within the myogenic CRMs in differentiating muscle cells. Our data suggests that variant sequences within MyoD-binding motifs and their multiplicity within the CRMs, as well as the spatial arrangement of the motifs, in combination confer binding affinity of MyoD, nucleosome occupancy and the epigenetic state of the myogenic CRMs. Our comparative genomic analysis of single nucleotide polymorphism (SNPs) across publically available data from 17 strains of laboratory mice suggests that variant sequences within MyoD-bound motifs, but not their genome-wide counterparts, are under selection. Taken together, our data suggests that variant sequences within MyoD-binding motifs are retained and have functional role to confer a dynamic range of affinities, enabling MyoD to establish a broad spectrum of activity across myogenic CRMs.

2018-01-02 | GSE80588 | GEO

MyoD induced enhancer RNA interacts with hnRNPL to activate target gene transcription during myogenic differentiation.

Project description:Emerging evidence supports roles of enhancer RNAs (eRNAs) in regulating target gene. Here, we study eRNA regulation and function during skeletal myoblast differentiation. We provide a panoramic view of enhancer transcription and categorization of eRNAs. Master transcription factor MyoD is crucial in activating eRNA production. Super enhancer (se) generated seRNA-1 and -2 promote myogenic differentiation in vitro and in vivo. seRNA-1 regulates expression levels of two nearby genes, myoglobin (Mb) and apolipoprotein L6 (Apol6), by binding to heterogeneous nuclear ribonucleoprotein L (hnRNPL). A CAAA tract on seRNA-1 is essential in mediating seRNA-1/hnRNPL binding and function. Disruption of seRNA-1-hnRNPL interaction attenuates Pol II and H3K36me3 deposition at the Mb locus, in coincidence with the reduction of its transcription. Furthermore, analyses of hnRNPL binding transcriptome-wide reveal its association with eRNAs is a general phenomenon in multiple cells. Collectively, we propose that eRNA-hnRNPL interaction represents a mechanism contributing to target mRNA activation.

| S-EPMC6923398 | biostudies-literature

Epigenetic analysis reveals the repressive function of MyoD during myogenic differentiation

Project description:We identify a subset of highly expressed genes related to muscle development, which show static H3K4me2 enrichment over the gene body and H3K4me3 enrichment towards the gene body during myogenic differentiation. This study reveals that MyoD significantly binds to this particular subset of genes and further systematic analysis shows the repressive role of MyoD. Interestingly, MyoD binds and down-regulates Patz1 which is important for maintaining pluripotency. These findings might provide a key regulatory mechanism to promote myogenic differentiation.

2017-06-14 | GSE63716 | GEO

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