Abstract
BackgroundThe nucleosome remodeling and deacetylase complex promotes cell fate decisions throughout embryonic development. Its core enzymatic subunit, the SNF2-like ATPase and Helicase Mi2, is well conserved throughout the eukaryotic kingdom and can be found in multiple and highly homologous copies in all vertebrates and some invertebrates. However, the reasons for such duplications and their implications for embryonic development are unknown.ResultsHere we studied the two C. elegans Mi2 homologues, LET-418 and CHD-3, which displayed redundant activities during early embryonic development. At the transcriptional level, these two Mi2 homologues redundantly repressed the expression of a large gene population. We found that LET-418 physically accumulated at TSS-proximal regions on transcriptionally active genomic targets involved in growth and development. Moreover, LET-418 acted redundantly with CHD-3 to block H3K4me3 deposition at these genes. Our study also revealed that LET-418 was partially responsible for recruiting Polycomb to chromatin and for promoting H3K27me3 deposition. Surprisingly, CHD-3 displayed opposite activities on Polycomb, as it was capable of moderating its LET-418-dependent recruitment and restricted the amount of H3K27me3 on the studied target genes.ConclusionAlthough closely homologous, LET-418 and CHD-3 showed both redundant and opposite functions in modulating the chromatin environment at developmental target genes. We identified the interplay between LET-418 and CHD-3 to finely tune the levels of histone marks at developmental target genes. More than just repressors, Mi2-containing complexes appear as subtle modulators of gene expression throughout development. The study of such molecular variations in vertebrate Mi2 counterparts might provide crucial insights to our understanding of the epigenetic control of early development.Electronic supplementary materialThe online version of this article (doi:10.1186/s13072-016-0091-3) contains supplementary material, which is available to authorized users.
Highlights
The nucleosome remodeling and deacetylase complex promotes cell fate decisions throughout embryonic development
Three Mi2 homologues are known for Arabidopsis, and we identified two putative CHD3 homologues in soybean (G. soja) and barrel clover (M. truncatula), but not in common rice (O. sativa) (Fig. 1a)
Mutations used in this study are indicated as deletions or point mutations. c, d Nomarski images of wild-type or chd-3(eh4) worms treated with control or let-418(RNAi), h post-egg laying at °C (c) or at the indicated time points (d)
Summary
The nucleosome remodeling and deacetylase complex promotes cell fate decisions throughout embryonic development. Throughout embryonic development, gene expression must be dynamically regulated in a time- and cell-specific manner to promote proper lineage commitment, tissue formation, and growth. The three vertebrate MTA family members evolved from successive genome duplications (reviewed in [7]) and are oppositely involved in mediating the response to the estrogen receptor (ER) in mammary tissue growth and during breast cancer invasion [8], suggesting that they achieve tissue-specific functions. A. thaliana expresses three Mi2 homologues, namely PICKLE (Pkl) and PICKLErelated proteins 1 and 2 (Pkr and Pkr2) [14], and pkl and pkr show redundant functions in suppressing embryonic lethality and establishing cell identity [15]. Let-418 and chd-3 act redundantly to promote proper differentiation of the vulval cell precursors P5.p and P7.p, implying that common functions of these proteins are required at later developmental stages and adulthood [17]
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