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Regulation of chromatin accessibility and gene expression in the developing hippocampal primordium by LIM-HD transcription factor LHX2

Show simple item record Suresh, Varun en_US Muralidharan, Bhavana en_US PRADHAN, SAURABH J. en_US Bose, Mahima en_US D'Souza, Leora en_US Parichha, Arpan en_US REDDY, PULI CHANDRAMOULI en_US GALANDE, SANJEEV en_US Tole, Shubha en_US 2023-08-31T12:40:00Z 2023-08-31T12:40:00Z 2023-08 en_US
dc.identifier.citation PLOS Genetics, 19(8): e1010874. en_US
dc.identifier.issn 1553-7404 en_US
dc.identifier.uri en_US
dc.description.abstract In the mammalian cerebral cortex, the hippocampal primordium (Hcp) occupies a discrete position in the dorsal telencephalic neuroepithelium adjacent to the neocortical primordium (Ncp). We examined transcriptomic and chromatin-level features that distinguish the Hcp from the Ncp in the mouse during the early neurogenic period, embryonic day (E)12.5. ATAC-seq revealed that the Hcp was more accessible than the Ncp at this stage. Motif analysis of the differentially accessible loci in these tissues revealed LHX2 as a candidate transcription factor for modulating gene regulatory networks (GRNs). We analyzed LHX2 occupancy profiles and compared these with transcriptomic data from control and Lhx2 mutant Hcp and Ncp at E12.5. Our results revealed that LHX2 directly regulates distinct genes in the Hcp and Ncp within a set of common pathways that control fundamental aspects of development namely pluripotency, axon pathfinding, Wnt, and Hippo signaling. Loss of Lhx2 caused a decrease in accessibility, specifically in hippocampal chromatin, suggesting that this factor may play a unique role in hippocampal development. We identified 14 genes that were preferentially enriched in the Hcp, for which LHX2 regulates both chromatin accessibility and mRNA expression, which have not thus far been examined in hippocampal development. Together, these results provide mechanistic insight into how LHX2 function in the Hcp may contribute to the process by which the hippocampus acquires features distinct from the neocortex. en_US
dc.language.iso en en_US
dc.publisher Public Library Science en_US
dc.subject Radial Glia en_US
dc.subject Neurons en_US
dc.subject Cells en_US
dc.subject Neurogenesis en_US
dc.subject Lineage en_US
dc.subject Cortex en_US
dc.subject Fate en_US
dc.subject PAX6 en_US
dc.subject EMX1 en_US
dc.subject 2023-AUG-WEEK4 en_US
dc.subject TOC-AUG-2023 en_US
dc.subject 2023 en_US
dc.title Regulation of chromatin accessibility and gene expression in the developing hippocampal primordium by LIM-HD transcription factor LHX2 en_US
dc.type Article en_US
dc.contributor.department Dept. of Biology en_US
dc.identifier.sourcetitle PLOS Genetics en_US
dc.publication.originofpublisher Foreign en_US

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