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Soares MAF, Soares DS, Teixeira V, et al. Hierarchical reactivation of transcription during mitosis-to-G1 transition by Brn2 and Ascl1 in neural stem cells. Genes Dev. 2021;35(13):1020-1034doi: 10.1101/gad.348174.120.
Soares, M. A. F., Soares, D. S., Teixeira, V., Heskol, A., Bressan, R. B., Pollard, S. M., Oliveira, R. A., & Castro, D. S. (2021). Hierarchical reactivation of transcription during mitosis-to-G1 transition by Brn2 and Ascl1 in neural stem cells. Genes & development, 35(13), 1020-1034. https://doi.org/10.1101/gad.348174.120
Soares, Mário A F, et al. "Hierarchical reactivation of transcription during mitosis-to-G1 transition by Brn2 and Ascl1 in neural stem cells." Genes & development vol. 35,13 (2021): 1020-1034. doi: https://doi.org/10.1101/gad.348174.120
Soares MAF, Soares DS, Teixeira V, Heskol A, Bressan RB, Pollard SM, Oliveira RA, Castro DS. Hierarchical reactivation of transcription during mitosis-to-G1 transition by Brn2 and Ascl1 in neural stem cells. Genes Dev. 2021 Jul 01;35(13):1020-1034. doi: 10.1101/gad.348174.120. Epub 2021 Jun 24. PMID: 34168041; PMCID: PMC8247608.
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Genes Dev. 2021 Jul 01;35(13):1020-1034. doi: 10.1101/gad.348174.120. Epub 2021 Jun 24.

Hierarchical reactivation of transcription during mitosis-to-G1 transition by Brn2 and Ascl1 in neural stem cells.

Genes & development

Mário A F Soares, Diogo S Soares, Vera Teixeira, Abeer Heskol, Raul Bardini Bressan, Steven M Pollard, Raquel A Oliveira, Diogo S Castro

Affiliations

  1. Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
  2. i3S Instituto de Investigação e Inovação em Saúde, IBMC Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal.
  3. Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh EH16 4UU, United Kingdom.

PMID: 34168041 PMCID: PMC8247608 DOI: 10.1101/gad.348174.120

Abstract

During mitosis, chromatin condensation is accompanied by a global arrest of transcription. Recent studies suggest transcriptional reactivation upon mitotic exit occurs in temporally coordinated waves, but the underlying regulatory principles have yet to be elucidated. In particular, the contribution of sequence-specific transcription factors (TFs) remains poorly understood. Here we report that Brn2, an important regulator of neural stem cell identity, associates with condensed chromatin throughout cell division, as assessed by live-cell imaging of proliferating neural stem cells. In contrast, the neuronal fate determinant Ascl1 dissociates from mitotic chromosomes. ChIP-seq analysis reveals that Brn2 mitotic chromosome binding does not result in sequence-specific interactions prior to mitotic exit, relying mostly on electrostatic forces. Nevertheless, surveying active transcription using single-molecule RNA-FISH against immature transcripts reveals differential reactivation kinetics for key targets of Brn2 and Ascl1, with transcription onset detected in early (anaphase) versus late (early G1) phases, respectively. Moreover, by using a mitotic-specific dominant-negative approach, we show that competing with Brn2 binding during mitotic exit reduces the transcription of its target gene

© 2021 Soares et al.; Published by Cold Spring Harbor Laboratory Press.

Keywords: Ascl1; Brn2; M-G1 transition; mitotic bookmarking; neural stem cell; transcription

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