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Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons
DLX transcription factors (TFs) are master regulators of the developing vertebrate brain, driving forebrain GABAergic neuronal differentiation. Ablation of Dlx1&2 alters expression of genes that are critical for forebrain GABAergic development. We integrated epigenomic and transcriptomic analyse...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750766/ https://www.ncbi.nlm.nih.gov/pubmed/31433982 http://dx.doi.org/10.1016/j.celrep.2019.07.022 |
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author | Lindtner, Susan Catta-Preta, Rinaldo Tian, Hua Su-Feher, Linda Price, James D. Dickel, Diane E. Greiner, Vanille Silberberg, Shanni N. McKinsey, Gabriel L. McManus, Michael T. Pennacchio, Len A. Visel, Axel Nord, Alex S. Rubenstein, John L.R. |
author_facet | Lindtner, Susan Catta-Preta, Rinaldo Tian, Hua Su-Feher, Linda Price, James D. Dickel, Diane E. Greiner, Vanille Silberberg, Shanni N. McKinsey, Gabriel L. McManus, Michael T. Pennacchio, Len A. Visel, Axel Nord, Alex S. Rubenstein, John L.R. |
author_sort | Lindtner, Susan |
collection | PubMed |
description | DLX transcription factors (TFs) are master regulators of the developing vertebrate brain, driving forebrain GABAergic neuronal differentiation. Ablation of Dlx1&2 alters expression of genes that are critical for forebrain GABAergic development. We integrated epigenomic and transcriptomic analyses, complemented with in situ hybridization (ISH), and in vivo and in vitro studies of regulatory element (RE) function. This revealed the DLX-organized gene regulatory network at genomic, cellular, and spatial levels in mouse embryonic basal ganglia. DLX TFs perform dual activating and repressing functions; the consequences of their binding were determined by the sequence and genomic context of target loci. Our results reveal and, in part, explain the paradox of widespread DLX binding contrasted with a limited subset of target loci that are sensitive at the epigenomic and transcriptomic level to Dlx1&2 ablation. The regulatory properties identified here for DLX TFs suggest general mechanisms by which TFs orchestrate dynamic expression programs underlying neurodevelopment. |
format | Online Article Text |
id | pubmed-6750766 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-67507662019-09-18 Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons Lindtner, Susan Catta-Preta, Rinaldo Tian, Hua Su-Feher, Linda Price, James D. Dickel, Diane E. Greiner, Vanille Silberberg, Shanni N. McKinsey, Gabriel L. McManus, Michael T. Pennacchio, Len A. Visel, Axel Nord, Alex S. Rubenstein, John L.R. Cell Rep Article DLX transcription factors (TFs) are master regulators of the developing vertebrate brain, driving forebrain GABAergic neuronal differentiation. Ablation of Dlx1&2 alters expression of genes that are critical for forebrain GABAergic development. We integrated epigenomic and transcriptomic analyses, complemented with in situ hybridization (ISH), and in vivo and in vitro studies of regulatory element (RE) function. This revealed the DLX-organized gene regulatory network at genomic, cellular, and spatial levels in mouse embryonic basal ganglia. DLX TFs perform dual activating and repressing functions; the consequences of their binding were determined by the sequence and genomic context of target loci. Our results reveal and, in part, explain the paradox of widespread DLX binding contrasted with a limited subset of target loci that are sensitive at the epigenomic and transcriptomic level to Dlx1&2 ablation. The regulatory properties identified here for DLX TFs suggest general mechanisms by which TFs orchestrate dynamic expression programs underlying neurodevelopment. 2019-08-20 /pmc/articles/PMC6750766/ /pubmed/31433982 http://dx.doi.org/10.1016/j.celrep.2019.07.022 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Lindtner, Susan Catta-Preta, Rinaldo Tian, Hua Su-Feher, Linda Price, James D. Dickel, Diane E. Greiner, Vanille Silberberg, Shanni N. McKinsey, Gabriel L. McManus, Michael T. Pennacchio, Len A. Visel, Axel Nord, Alex S. Rubenstein, John L.R. Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons |
title | Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons |
title_full | Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons |
title_fullStr | Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons |
title_full_unstemmed | Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons |
title_short | Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons |
title_sort | genomic resolution of dlx-orchestrated transcriptional circuits driving development of forebrain gabaergic neurons |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750766/ https://www.ncbi.nlm.nih.gov/pubmed/31433982 http://dx.doi.org/10.1016/j.celrep.2019.07.022 |
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