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Dev Biol 2022 Dec 01;492:14-24. doi: 10.1016/j.ydbio.2022.09.008.
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Ash2l, an obligatory component of H3K4 methylation complexes, regulates neural crest development.

Mohammadparast S , Chang C .

The vertebrate nervous system develops from embryonic neural plate and neural crest. Although genetic mechanisms governing vertebrate neural development have been investigated in depth, epigenetic regulation of this process remains less understood. Redundancy of epigenetic factors and early lethality of animals deficient in critical epigenetic components pose major challenges in characterization of epigenetic factors in vertebrate neural development. In this study, we use the amphibian model Xenopus laevis to investigate the roles of non-redundant, obligatory components of all histone H3K4 activating methylation complexes (COMPASS, also known as SET1/MLL complexes) in early neural development. The two genes that we focus on, Ash2l and Dpy30, regulate mesendodermal differentiation in mouse embryonic stem cells and cause early embryonic lethality when removed from mouse embryos. Using targeted knockdown of the genes in dorsal ectoderm of Xenopus that gives rise to future nervous system, we show here that ash2l and dpy30 are required for neural and neural crest marker expression in Xenopus late neurula embryos but are dispensable for early neural and neural plate border gene expression. Co-immunoprecipitation assays reveal that Dpy30 and Ash2L associate with the neural plate border transcription factors, such as Msx1 and Tfap2a. Chromatin immunoprecipitation (ChIP) assay further demonstrates that Ash2L and the H3K4me3 active histone mark accumulate at the promoter regions of the neural crest gene sox10 in a Tfap2a-dependent manner. Collectively, our data suggest that Ash2l and Dpy30 interact with specific transcription factors to recruit COMPASS complexes to the regulatory regions of neural crest specification genes to control their expression and influence development of the nervous system during vertebrate embryogenesis.

PubMed ID: 36162552
Article link: Dev Biol
Grant support: [+]

Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: ash2l dlx3 dlx5 dpy30 ets1 foxd3 h2bc21 msx1 ncam1 nrp1 pax3 pax7 snai1 snai2 sox10 sox2 sox3 sox9 tfap2a twist1 zic1
GO keywords: neural crest formation [+]
Morpholinos: ash2l MO1 ash2l MO2 dpy30 MO1

Article Images: [+] show captions