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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.

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


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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