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Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis
- Source :
- Cell Reports, Cell Reports, 2015, 10 (9), pp.1544-1556. ⟨10.1016/j.celrep.2015.02.025⟩, Cell Reports, Elsevier Inc, 2015, 10 (9), pp.1544-1556. ⟨10.1016/j.celrep.2015.02.025⟩, Repositório Científico de Acesso Aberto de Portugal, Repositório Científico de Acesso Aberto de Portugal (RCAAP), instacron:RCAAP, Cell Reports, Vol 10, Iss 9, Pp 1544-1556 (2015)
- Publication Year :
- 2015
- Publisher :
- HAL CCSD, 2015.
-
Abstract
- Summary 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.<br />Graphical Abstract<br />Highlights • Genome-wide binding of Ascl1 correlates with transcription activation • Ascl1 can bind to both open and closed chromatin in proliferating cells • Ascl1 promotes local chromatin accessibility at its target sites • Chromatin dynamics at Ascl1 sites regulates temporal progression of its program<br />The proneural transcription factor Ascl1 sequentially activates target genes in proliferating and differentiating progenitors during neurogenesis. Here Raposo et al. show that Ascl1 binds closed and open chromatin in proliferating cells. Binding to closed chromatin promotes accessibility and activation of differentiation specific genes. Thus, dynamics of chromatin landscape at Ascl1 target regions regulate the temporal onset of Ascl1 targets.
- Subjects :
- Genetics
0303 health sciences
Neurogenesis
DNA
Biology
General Biochemistry, Genetics and Molecular Biology
Chromatin remodeling
Article
Cell biology
Chromatin
03 medical and health sciences
0302 clinical medicine
lcsh:Biology (General)
[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Ascl1
Scaffold/matrix attachment region
Enhancer
lcsh:QH301-705.5
Transcription factor
030217 neurology & neurosurgery
ChIA-PET
030304 developmental biology
Bivalent chromatin
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Database :
- OpenAIRE
- Journal :
- Cell Reports, Cell Reports, 2015, 10 (9), pp.1544-1556. ⟨10.1016/j.celrep.2015.02.025⟩, Cell Reports, Elsevier Inc, 2015, 10 (9), pp.1544-1556. ⟨10.1016/j.celrep.2015.02.025⟩, Repositório Científico de Acesso Aberto de Portugal, Repositório Científico de Acesso Aberto de Portugal (RCAAP), instacron:RCAAP, Cell Reports, Vol 10, Iss 9, Pp 1544-1556 (2015)
- Accession number :
- edsair.doi.dedup.....11c7f2a5e370c1c23e233a175676f6e7