The landscape of pioneer factor activity reveals the mechanisms of chromatin reprogramming and genome activation.

Autor:	Miao L; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: liyun.miao@yale.edu., Tang Y; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA., Bonneau AR; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA., Chan SH; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA., Kojima ML; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA., Pownall ME; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA., Vejnar CE; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA., Gao F; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA., Krishnaswamy S; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Computer Science, Yale University School of Medicine, New Haven, CT 06510, USA., Hendry CE; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA., Giraldez AJ; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Yale 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.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2022 Mar 03; Vol. 82 (5), pp. 986-1002.e9. Date of Electronic Publication: 2022 Feb 18.
DOI:	10.1016/j.molcel.2022.01.024
Abstrakt:	Upon fertilization, embryos undergo chromatin reprogramming and genome activation; however, the mechanisms that regulate these processes are poorly understood. Here, we generated a triple mutant for Nanog, Pou5f3, and Sox19b (NPS) in zebrafish and found that NPS pioneer chromatin opening at >50% of active enhancers. NPS regulate acetylation across core histones at enhancers and promoters, and their function in gene activation can be bypassed by recruiting histone acetyltransferase to individual genes. NPS pioneer chromatin opening individually, redundantly, or additively depending on sequence context, and we show that high nucleosome occupancy facilitates NPS pioneering activity. Nucleosome position varies based on the input of different transcription factors (TFs), providing a flexible platform to modulate pioneering activity. Altogether, our results illuminate the sequence of events during genome activation and offer a conceptual framework to understand how pioneer factors interpret the genome and integrate different TF inputs across cell types and developmental transitions. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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