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LHX2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11

Muralidharan, B; Khatri, Z; Maheshwari, U; Gupta, R; Roy, B; Pradhan, SJ; Karmodiya, K; ... Tole, S; + view all (2017) LHX2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11. Journal of Neuroscience , 37 (1) pp. 194-203. 10.1523/JNEUROSCI.2836-16.2017. Green open access

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Abstract

In the developing cerebral cortex, sequential transcriptional programs take neuroepithelial cells from proliferating progenitors to differentiated neurons with unique molecular identities. The regulatory changes that occur in the chromatin of the progenitors are not well understood. During deep layer neurogenesis, we show that transcription factor LHX2 binds to distal regulatory elements of Fezf2 and Sox11, critical determinants of neuron subtype identity in the mouse neocortex. We demonstrate that LHX2 binds to the nucleosome remodeling and histone deacetylase histone remodeling complex subunits LSD1, HDAC2, and RBBP4, which are proximal regulators of the epigenetic state of chromatin. When LHX2 is absent, active histone marks at the Fezf2 and Sox11 loci are increased. Loss of LHX2 produces an increase, and overexpression of LHX2 causes a decrease, in layer 5 Fezf2 and CTIP2-expressing neurons. Our results provide mechanistic insight into how LHX2 acts as a necessary and sufficient regulator of genes that control cortical neuronal subtype identity.

Type: Article
Title: LHX2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11
Open access status: An open access version is available from UCL Discovery
DOI: 10.1523/JNEUROSCI.2836-16.2017
Publisher version: https://doi.org/10.1523/JNEUROSCI.2836-16.2016
Language: English
Additional information: Copyright © 2017 Muralidharan et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License Creative Commons Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords: cell fate; chromatin; epigenetics; lamination; progenitor; specification
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10033952
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