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Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment

ABSTRACT: Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment

PROVIDER: PRJNA339562 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR4044924.fastq.gz	Fastqsanger.gz
	SRR4044924_1.fastq.gz	Fastqsanger.gz
	SRR4044924_2.fastq.gz	Fastqsanger.gz
	SRR4044925.fastq.gz	Fastqsanger.gz
	SRR4044926.fastq.gz	Fastqsanger.gz

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Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment [microarray]

Project description:Organization of the genome in 3D nuclear-space is known to play a crucial role in regulation of gene expression. However, the chromatin architecture that impinges on the B cell-fate choice of multi-potent progenitors remains unclear. By employing in situ Hi-C, we have identified distinct sets of genomic loci that undergo a developmental switch between permissive and repressive compartments during B-cell fate commitment. Intriguingly, we show that topologically associating domains (TADs) represent co-regulated subunits of chromatin and display considerable structural alterations as a result of changes in the cis-regulatory interaction landscape. The extensive rewiring of cis-regulatory interactions is closely associated with differential gene expression programs. Further, we demonstrate the regulatory role of Ebf1 and its downstream factor, Pax5, in chromatin reorganization and transcription regulation. Together, our studies reveal that alterations in promoter and cis-regulatory interactions underlie changes in higher-order chromatin architecture, which in turn determines cell-identity and cell-type specific gene expression patterns.

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Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment [Hi-C]

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Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment.

Project description:Genome organization in 3D nuclear-space is important for regulation of gene expression. However, the alterations of chromatin architecture that impinge on the B cell-fate choice of multi-potent progenitors are still unclear. By integrating in situ Hi-C analyses with epigenetic landscapes and genome-wide expression profiles, we tracked the changes in genome architecture as the cells transit from a progenitor to a committed state. We identified the genomic loci that undergo developmental switch between A and B compartments during B-cell fate determination. Furthermore, although, topologically associating domains (TADs) are stable, a significant number of TADs display structural alterations that are associated with changes in cis-regulatory interaction landscape. Finally, we demonstrate the potential roles for Ebf1 and its downstream factor, Pax5, in chromatin reorganization and transcription regulation. Collectively, our studies provide a general paradigm of the dynamic relationship between chromatin reorganization and lineage-specific gene expression pattern that dictates cell-fate determination.

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Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment

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