Brd4 and P300 Confer Transcriptional Competency during Zygotic Genome Activation

• Published in: Developmental cell Vol. 49; no. 6; pp. 867 - 881.e8
• Main Authors: Chan, Shun Hang, Tang, Yin, Miao, Liyun, Darwich-Codore, Hiba, Vejnar, Charles E., Beaudoin, Jean-Denis, Musaev, Damir, Fernandez, Juan P., Benitez, Maria D.J., Bazzini, Ariel A., Moreno-Mateos, Miguel A., Giraldez, Antonio J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.06.2019
• Subjects: Animals; cell reprogramming; E1A-Associated p300 Protein - genetics; E1A-Associated p300 Protein - metabolism; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - metabolism; Embryonic Development; Gene Expression Regulation, Developmental; Genome; genome activation; histone modifications; live imaging; maternal-to-zygotic transition; Regulatory Sequences, Nucleic Acid; transcription; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional Activation; Transcriptome; zebrafish; Zebrafish - embryology; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; Zygote - cytology; Zygote - metabolism; zygotic genome activation; live imaging; maternal-to-zygotic transition; cell reprogramming; transcription; embryonic development; genome activation; histone modifications; zebrafish; transcriptional activation; zygotic genome activation
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2019.05.037

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. [Display omitted] •Live imaging reveals that the first zygotic transcription is stochastic in zebrafish•Transcriptional competency depends on developmental time, independent of cell division•P300 and Brd4 activity are necessary for genome activation and zygotic development•P300 and BRD4 are sufficient to trigger premature genome activation Genome activation after fertilization is a cornerstone of development. Chan et al. show that the writers and readers of histone acetylation, p300 and Brd4, are limiting factors required to activate the genome. Genome activation is characterized by a gain of H3K27Ac acetylation and a stochastic activation at the first transcribed locus miR-430.