Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis

Alexandre A.S.F. Raposo; Francisca F. Vasconcelos; Daniela Drechsel; Corentine Marie; Caroline Johnston; Dirk Dolle; Angela Bithell; Sébastien Gillotin; Debbie L.C. van den Berg; Laurence Ettwiller; Paul Flicek; Gregory E. Crawford; Carlos M. Parras; Benedikt Berninger; Noel J. Buckley; François Guillemot; Diogo S. Castro

doi:10.1016/j.celrep.2015.02.025

Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis

Alexandre A.S.F. Raposo, Francisca F. Vasconcelos, Daniela Drechsel, Corentine Marie, Caroline Johnston, Dirk Dolle, Angela Bithell, Sébastien Gillotin, Debbie L.C. van den Berg, Laurence Ettwiller, Paul Flicek, Gregory E. Crawford, Carlos M. Parras, Benedikt Berninger, Noel J. Buckley, François Guillemot, Diogo S. Castro^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

142 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1544-1556
Number of pages	13
Journal	Cell Reports
Volume	10
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2015.02.025
Publication status	Published - 10 Mar 2015

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Raposo, A. A. S. F., Vasconcelos, F. F., Drechsel, D., Marie, C., Johnston, C., Dolle, D., Bithell, A., Gillotin, S., van den Berg, D. L. C., Ettwiller, L., Flicek, P., Crawford, G. E., Parras, C. M., Berninger, B., Buckley, N. J., Guillemot, F., & Castro, D. S. (2015). Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis. Cell Reports, 10(9), 1544-1556. https://doi.org/10.1016/j.celrep.2015.02.025

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title = "Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis",

abstract = "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.",

author = "Raposo, {Alexandre A.S.F.} and Vasconcelos, {Francisca F.} and Daniela Drechsel and Corentine Marie and Caroline Johnston and Dirk Dolle and Angela Bithell and S{\'e}bastien Gillotin and {van den Berg}, {Debbie L.C.} and Laurence Ettwiller and Paul Flicek and Crawford, {Gregory E.} and Parras, {Carlos M.} and Benedikt Berninger and Buckley, {Noel J.} and Fran{\c c}ois Guillemot and Castro, {Diogo S.}",

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Raposo, AASF, Vasconcelos, FF, Drechsel, D, Marie, C, Johnston, C, Dolle, D, Bithell, A, Gillotin, S, van den Berg, DLC, Ettwiller, L, Flicek, P, Crawford, GE, Parras, CM, Berninger, B, Buckley, NJ, Guillemot, F & Castro, DS 2015, 'Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis', Cell Reports, vol. 10, no. 9, pp. 1544-1556. https://doi.org/10.1016/j.celrep.2015.02.025

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AU - Raposo, Alexandre A.S.F.

AU - Vasconcelos, Francisca F.

AU - Drechsel, Daniela

AU - Marie, Corentine

AU - Johnston, Caroline

AU - Dolle, Dirk

AU - Bithell, Angela

AU - Gillotin, Sébastien

AU - van den Berg, Debbie L.C.

AU - Ettwiller, Laurence

AU - Flicek, Paul

AU - Crawford, Gregory E.

AU - Parras, Carlos M.

AU - Berninger, Benedikt

AU - Buckley, Noel J.

AU - Guillemot, François

AU - Castro, Diogo S.

PY - 2015/3/10

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AB - 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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Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis

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