DLX1 and the NuRD complex cooperate in enhancer decommissioning and transcriptional repression
Year: 2022
Type: article
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.
Source: Development
DOI: 10.1242/dev.199508
Authors: James D. Price, Susan Lindtner, Athena Ypsilanti, Fadya Binyameen, Jeffrey R. Johnson, Billy W. Newton, Nevan J. Krogan, John L. R. Rubenstein
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Human Genome Research Institute, National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development, National Institute of Dental and Craniofacial Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Research Project: Genome-Wide Atlas of Craniofacial Transcriptional Enhancers, A High-Resolution Enhancer Atlas of the Developing Forebrain, Combinatorial Regulation of Gene Networks During Cardiac Development and Disease, Comparative Genomic Resources for CV Research, Genetic Regulation of Telencephalon Development, Predoctoral Training in Developmental Biology, Functionally Assessing Transcriptional Enhancers In Vivo
OpenAlex ID: W4282841968