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Title: Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons

The embryonic basal ganglia generates multiple projection neurons and interneuron subtypes from distinct progenitor domains. Combinatorial interactions of transcription factors and chromatin are thought to regulate gene expression. In the medial ganglionic eminence, the NKX2-1 transcription factor controls regional identity and, with LHX6, is necessary to specify pallidal projection neurons and forebrain interneurons. Here, we dissected the molecular functions of NKX2-1 by defining its chromosomal binding, regulation of gene expression, and epigenetic state. NKX2-1 binding at distal regulatory elements led to a repressed epigenetic state and transcriptional repression in the ventricular zone. Conversely, NKX2-1 is required to establish a permissive chromatin state and transcriptional activation in the sub-ventricular and mantle zones. Moreover, combinatorial binding of NKX2-1 and LHX6 promotes transcriptionally permissive chromatin and activates genes expressed in cortical migrating interneurons. Our integrated approach gives a foundation for elucidating transcriptional networks guiding the development of the MGE and its descendants.
Authors:
 [1] ;  [1] ;  [1] ;  [2] ;  [1] ;  [1] ;  [1] ;  [3] ;  [2] ;  [1]
  1. Univ. of California, San Francisco, CA (United States)
  2. Univ. of California, Davis, CA (United States)
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Univ. of California, Merced, CA (United States)
Publication Date:
Grant/Contract Number:
AC02-05CH11231; AC02- 05CH11231
Type:
Published Article
Journal Name:
Neuron
Additional Journal Information:
Journal Volume: 91; Journal Issue: 6; Journal ID: ISSN 0896-6273
Publisher:
Cell Press / Elsevier
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1393685
Alternate Identifier(s):
OSTI ID: 1393077

Sandberg, Magnus, Flandin, Pierre, Silberberg, Shanni, Su-Feher, Linda, Price, James D., Hu, Jia Sheng, Kim, Carol, Visel, Axel, Nord, Alex S., and Rubenstein, John L. R.. Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons. United States: N. p., Web. doi:10.1016/j.neuron.2016.08.020.
Sandberg, Magnus, Flandin, Pierre, Silberberg, Shanni, Su-Feher, Linda, Price, James D., Hu, Jia Sheng, Kim, Carol, Visel, Axel, Nord, Alex S., & Rubenstein, John L. R.. Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons. United States. doi:10.1016/j.neuron.2016.08.020.
Sandberg, Magnus, Flandin, Pierre, Silberberg, Shanni, Su-Feher, Linda, Price, James D., Hu, Jia Sheng, Kim, Carol, Visel, Axel, Nord, Alex S., and Rubenstein, John L. R.. 2016. "Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons". United States. doi:10.1016/j.neuron.2016.08.020.
@article{osti_1393685,
title = {Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons},
author = {Sandberg, Magnus and Flandin, Pierre and Silberberg, Shanni and Su-Feher, Linda and Price, James D. and Hu, Jia Sheng and Kim, Carol and Visel, Axel and Nord, Alex S. and Rubenstein, John L. R.},
abstractNote = {The embryonic basal ganglia generates multiple projection neurons and interneuron subtypes from distinct progenitor domains. Combinatorial interactions of transcription factors and chromatin are thought to regulate gene expression. In the medial ganglionic eminence, the NKX2-1 transcription factor controls regional identity and, with LHX6, is necessary to specify pallidal projection neurons and forebrain interneurons. Here, we dissected the molecular functions of NKX2-1 by defining its chromosomal binding, regulation of gene expression, and epigenetic state. NKX2-1 binding at distal regulatory elements led to a repressed epigenetic state and transcriptional repression in the ventricular zone. Conversely, NKX2-1 is required to establish a permissive chromatin state and transcriptional activation in the sub-ventricular and mantle zones. Moreover, combinatorial binding of NKX2-1 and LHX6 promotes transcriptionally permissive chromatin and activates genes expressed in cortical migrating interneurons. Our integrated approach gives a foundation for elucidating transcriptional networks guiding the development of the MGE and its descendants.},
doi = {10.1016/j.neuron.2016.08.020},
journal = {Neuron},
number = 6,
volume = 91,
place = {United States},
year = {2016},
month = {9}
}