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Nucleic Acids Res. 2017 Nov 2;45(19):11070-11087. doi: 10.1093/nar/gkx722.

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

Author information

1
Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
2
Institute for Stem Cell Biology and Regenerative Medicine, National Centre for Biological Sciences, Bangalore 560065, India.

Abstract

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.

PMID:
28977418
PMCID:
PMC5737614
DOI:
10.1093/nar/gkx722
[Indexed for MEDLINE]
Free PMC Article

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