Boya Ravi, Yadavalli Anurupa Devi, Nikhat Sameena, Kurukuti Sreenivasulu, Palakodeti Dasaradhi, Pongubala Jagan M R
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.
Nucleic Acids Res. 2017 Nov 2;45(19):11070-11087. doi: 10.1093/nar/gkx722.
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.
三维核空间中的基因组组织对于基因表达调控至关重要。然而，影响多能祖细胞B细胞命运选择的染色质结构改变仍不清楚。通过将原位Hi-C分析与表观遗传景观和全基因组表达谱相结合，我们追踪了细胞从祖细胞转变为定向分化状态时基因组结构的变化。我们确定了在B细胞命运决定过程中在A和B区室之间发生发育转换的基因组位点。此外，尽管拓扑相关结构域（TADs）是稳定的，但大量TADs显示出与顺式调控相互作用景观变化相关的结构改变。最后，我们证明了Ebf1及其下游因子Pax5在染色质重组和转录调控中的潜在作用。总的来说，我们的研究提供了一个染色质重组与决定细胞命运的谱系特异性基因表达模式之间动态关系的一般范例。
