@article{fb239a1490f143969d63e2af980995a5,
title = "DLX1 and the NuRD complex cooperate in enhancer decommissioning and transcriptional repression",
abstract = "In the developing subpallium, the fate decision between neurons and glia is driven by expression of Dlx1/2 or Olig1/2, respectively, two sets of transcription factors with a mutually repressive relationship. The mechanism by which Dlx1/2 repress progenitor and oligodendrocyte fate, while promoting transcription of genes needed for differentiation, is not fully understood. We identified a motif within DLX1 that binds RBBP4, a NuRD complex subunit. ChIP-seq studies of genomic occupancy of DLX1 and six different members of the NuRD complex show that DLX1 and NuRD colocalize to putative regulatory elements enriched near other transcription factor genes. Loss of Dlx1/2 leads to dysregulation of genome accessibility at putative regulatory elements near genes repressed by Dlx1/2, including Olig2. Consequently, heterozygosity of Dlx1/2 and Rbbp4 leads to an increase in the production of OLIG2+ cells. These findings highlight the importance of the interplay between transcription factors and chromatin remodelers in regulating cell-fate decisions.",
keywords = "Chromatin, DLX, Enhancer, Mouse, NuRD complex, Subpallium, Transcription factor",
author = "Price, {James D.} and Susan Lindtner and Athena Ypsilanti and Fadya Binyameen and Johnson, {Jeffrey R.} and Newton, {Billy W.} and Krogan, {Nevan J.} and Rubenstein, {John L.R.}",
note = "Funding Information: This work was supported by research grants from Nina Ireland (to J.L.R.R.), the National Institute of Mental Health (R01MH049428 to J.L.R.R.), the National Heart, Lung, and Blood Institute (P01 HL146366 to N.J.K.) and the National Institute of Child Health and Human Development (Predoctoral Training in Developmental Biology; T32HD007470 to J.D.P.). Deposited in PMC for release after 12 months. Funding Information: Thank you to Dr Brian Black and Dr Benoit Bruneau for their guidance and scientific contributions throughout the project. To Gwendolyn Jang and Swetansu Hota for their assistance with protocols and reagents used in immunoprecipitation, Dr Alex Nord and Rinaldo Catta-Preta for their support with bioinformatic analysis, and Diane Dickel, Jennifer Akiyama and the rest of the team with the VISTA Enhancer Browser for their assistance with obtaining transient transgenic enhancer embryos. Funding for the VISTA Enhancer Browser was provided by grant HL066681, Berkeley-PGA, under the Programs for Genomic Applications, funded by National Heart, Lung, and Blood Institute, HG003988 funded by National Human Genome Research Institute, NS062859 funded by National Institute of Neurological Disorders and Stroke, and DE020060 funded by National Institute of Dental and Craniofacial Research. This work was supported by research grants from Nina Ireland (to J.L.R.R.), the National Institute of Mental Health (R01MH049428 to J.L.R.R.), the National Heart, Lung, and Blood Institute (P01 HL146366 to N.J.K.) and the National Institute of Child Health and Human Development (Predoctoral Training in Developmental Biology; T32HD007470 to J.D.P.). Deposited in PMC for release after 12 months. Funding Information: Thank you to Dr Brian Black and Dr Benoit Bruneau for their guidance and scientific contributions throughout the project. To Gwendolyn Jang and Swetansu Hota for their assistance with protocols and reagents used in immunoprecipitation, Dr Alex Nord and Rinaldo Catta-Preta for their support with bioinformatic analysis, and Diane Dickel, Jennifer Akiyama and the rest of the team with the VISTA Enhancer Browser for their assistance with obtaining transient transgenic enhancer embryos. Funding for the VISTA Enhancer Browser was provided by grant HL066681, Berkeley-PGA, under the Programs for Genomic Applications, funded by National Heart, Lung, and Blood Institute, HG003988 funded by National Human Genome Research Institute, NS062859 funded by National Institute of Neurological Disorders and Stroke, and DE020060 funded by National Institute of Dental and Craniofacial Research. Publisher Copyright: {\textcopyright} 2022. Published by The Company of Biologists Ltd.",
year = "2022",
month = jun,
doi = "10.1242/dev.199508",
language = "English",
volume = "149",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "11",
}