Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis

The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how Ascl1 interacts with the chromatin landscape to regulate gene expression when promo...

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Main Authors: Raposo, A, Vasconcelos, F, Drechsel, D, Marie, C, Johnston, C, Dolle, D, Bithell, A, Gillotin, S, van der Berg, D, Ettwiller, L, Flicek, P, Crawford, G, Parras, C, Berninger, B, Buckley, N, Guillemot, F, Castro, D
Format: Journal article
Published: Elsevier 2015
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author Raposo, A
Vasconcelos, F
Drechsel, D
Marie, C
Johnston, C
Dolle, D
Bithell, A
Gillotin, S
van der Berg, D
Ettwiller, L
Flicek, P
Crawford, G
Parras, C
Berninger, B
Buckley, N
Guillemot, F
Castro, D
author2 Raposo, A
author_facet Raposo, A
Raposo, A
Vasconcelos, F
Drechsel, D
Marie, C
Johnston, C
Dolle, D
Bithell, A
Gillotin, S
van der Berg, D
Ettwiller, L
Flicek, P
Crawford, G
Parras, C
Berninger, B
Buckley, N
Guillemot, F
Castro, D
author_sort Raposo, A
collection OXFORD
description The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how Ascl1 interacts with the chromatin landscape to regulate gene expression when promoting neuronal differentiation. We find that Ascl1 binding occurs mostly at distal enhancers and is associated with activation of gene transcription. Surprisingly, the accessibility of Ascl1 to its binding sites in neural stem/progenitor cells remains largely unchanged throughout their differentiation, as Ascl1 targets regions of both readily accessible and closed chromatin in proliferating cells. Moreover, binding of Ascl1 often precedes an increase in chromatin accessibility and the appearance of new regions of open chromatin, associated with de novo gene expression during differentiation. Our results reveal a function of Ascl1 in promoting chromatin accessibility during neurogenesis, linking the chromatin landscape at Ascl1 target regions with the temporal progression of its transcriptional program.
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spelling oxford-uuid:19460b06-8d12-404f-b24f-1203923061b82022-03-26T10:48:09ZAscl1 coordinately regulates gene expression and the chromatin landscape during neurogenesisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:19460b06-8d12-404f-b24f-1203923061b8Symplectic Elements at OxfordElsevier2015Raposo, AVasconcelos, FDrechsel, DMarie, CJohnston, CDolle, DBithell, AGillotin, Svan der Berg, DEttwiller, LFlicek, PCrawford, GParras, CBerninger, BBuckley, NGuillemot, FCastro, DRaposo, AThe proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how Ascl1 interacts with the chromatin landscape to regulate gene expression when promoting neuronal differentiation. We find that Ascl1 binding occurs mostly at distal enhancers and is associated with activation of gene transcription. Surprisingly, the accessibility of Ascl1 to its binding sites in neural stem/progenitor cells remains largely unchanged throughout their differentiation, as Ascl1 targets regions of both readily accessible and closed chromatin in proliferating cells. Moreover, binding of Ascl1 often precedes an increase in chromatin accessibility and the appearance of new regions of open chromatin, associated with de novo gene expression during differentiation. Our results reveal a function of Ascl1 in promoting chromatin accessibility during neurogenesis, linking the chromatin landscape at Ascl1 target regions with the temporal progression of its transcriptional program.
spellingShingle Raposo, A
Vasconcelos, F
Drechsel, D
Marie, C
Johnston, C
Dolle, D
Bithell, A
Gillotin, S
van der Berg, D
Ettwiller, L
Flicek, P
Crawford, G
Parras, C
Berninger, B
Buckley, N
Guillemot, F
Castro, D
Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis
title Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis
title_full Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis
title_fullStr Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis
title_full_unstemmed Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis
title_short Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis
title_sort ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis
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