Raja, Desingu Ayyappa and Subramaniam, Yogaspoorthi and Aggarwal, Ayush and Gotherwal, Vishvabandhu and Babu, Aswini and Tanwar, Jyoti and Motiani, Rajender K. and Sivasubbu, Sridhar and Gokhale, Rajesh S. and Natarajan, Vivek T. (2020) Histone variant dictates fate biasing of neural crest cells to melanocyte lineage. Development, 147 (5). dev182576. ISSN 0950-1991

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Abstract

In the neural crest lineage, progressive fate restriction and stem cell assignment are crucial for both development and regeneration. Whereas fate commitment events have distinct transcriptional footprints, fate biasing is often transitory and metastable, and is thought to be moulded by epigenetic programmes. Therefore, the molecular basis of specification is difficult to define. In this study, we established a role for a histone variant, H2a.z.2, in specification of the melanocyte lineage from multipotent neural crest cells. H2a.z.2 silencing reduces the number of melanocyte precursors in developing zebrafish embryos and from mouse embryonic stem cells in vitro. We demonstrate that this histone variant occupies nucleosomes in the promoter of the key melanocyte determinant mitf, and enhances its induction. CRISPR/Cas9-based targeted mutagenesis of this gene in zebrafish drastically reduces adult melanocytes, as well as their regeneration. Thereby, our study establishes the role of a histone variant upstream of the core gene regulatory network in the neural crest lineage. This epigenetic mark is a key determinant of cell fate and facilitates gene activation by external instructive signals, thereby establishing melanocyte fate identity.

Item Type:	Article
Subjects:	Biomedical Science
Depositing User:	RCB Library
Date Deposited:	25 Jun 2020 12:05
Last Modified:	25 Jun 2020 12:05
URI:	http://rcb.sciencecentral.in/id/eprint/283

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