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Dev Cell. 2019 Jun 17;49(6):867-881.e8. doi: 10.1016/j.devcel.2019.05.037.

Brd4 and P300 Confer Transcriptional Competency during Zygotic Genome Activation.

Author information

1
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
2
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
3
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: mamormat@upo.es.
4
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Stem Cell Center, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: antonio.giraldez@yale.edu.

Abstract

The awakening of the genome after fertilization is a cornerstone of animal development. However, the mechanisms that activate the silent genome after fertilization are poorly understood. Here, we show that transcriptional competency is regulated by Brd4- and P300-dependent histone acetylation in zebrafish. Live imaging of transcription revealed that genome activation, beginning at the miR-430 locus, is gradual and stochastic. We show that genome activation does not require slowdown of the cell cycle and is regulated through the translation of maternally inherited mRNAs. Among these, the enhancer regulators P300 and Brd4 can prematurely activate transcription and restore transcriptional competency when maternal mRNA translation is blocked, whereas inhibition of histone acetylation blocks genome activation. We conclude that P300 and Brd4 are sufficient to trigger genome-wide transcriptional competency by regulating histone acetylation on the first zygotic genes in zebrafish. This mechanism is critical for initiating zygotic development and developmental reprogramming.

KEYWORDS:

cell reprogramming; embryonic development; genome activation; histone modifications; live imaging; maternal-to-zygotic transition; transcription; transcriptional activation; zebrafish; zygotic genome activation

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