H3K23me2 is a new heterochromatic mark inCaenorhabditis elegans

Abstract

Genome-wide analyses in Caenorhabditis elegans show that post-translational modifications (PTMs) of histones are evolutionary conserved and distributed along functionally distinct genomic domains. However, a global profile of PTMs and their co-occurrence on the same histone tail has not been described in this organism. We used mass spectrometry based middle-down proteomics to analyze histone H3 N-terminal tails from C. elegans embryos for the presence, the relative abundance and the potential cross-talk of co-existing PTMs. This analysis highlighted that the lysine 23 of histone H3 (H3K23) is extensively modified by methylation and that tri-methylated H3K9 (H3K9me3) is exclusively detected on histone tails with di-methylated H3K23 (H3K23me2). Chromatin immunoprecipitation approaches revealed a positive correlation between H3K23me2 and repressive marks. By immunofluorescence analyses, H3K23me2 appears differentially regulated in germ and somatic cells, in part by the action of the histone demethylase JMJD-1.2. H3K23me2 is enriched in heterochromatic regions, localizing in H3K9me3 and heterochromatin protein like-1 (HPL-1)-positive foci. Biochemical analyses indicated that HPL-1 binds to H3K23me2 and interacts with a conserved CoREST repressive complex. Thus, our study suggests that H3K23me2 defines repressive domains and contributes to organizing the genome in distinct heterochromatic regions during embryogenesis.

JMJD-1.2/PHF8 controls axon guidance by regulating Hedgehog-like signaling

“…PHF8 shares high homology with the C. elegans JMJD-1.2 protein, which retains both the JmjC and the PHD finger domains. However, the catalytic activity of JMJD-1.2 appears to differ from that of the mammalian counterpart, as several studies have shown its ability to demethylate not only H3K9me2, but also H3K27me2 and H3K23me2, both in vitro and in vivo (Kleine-Kohlbrecher et al, 2010;Lin et al, 2010;Vandamme et al, 2015). In agreement with the role of PHF8 in neuronal processes, JMJD-1.2 is required for normal locomotion in C. elegans, highlighting the importance of this protein in the establishment of neuronal functionalities (Kleine-Kohlbrecher et al, 2010).…”

“…The JmjC domain of JMJD-1.2 has been shown to demethylate H3K9me2, H3K27me2 and H3K23me2 in vitro and in vivo and, accordingly, increased signal of these post-translational modifications is found in the tm3713 mutant strain (KleineKohlbrecher et al, 2010;Lin et al, 2010;Vandamme et al, 2015). To test the relevance of JMJD-1.2 enzymatic activity in axon guidance, we mutated the JmjC domain (Fig.…”

Meiotic recombination and the crossover assurance checkpoint in Caenorhabditis elegans

“…An intriguing possibility is that a recently discovered mark, H3K23me3, which is strongly enriched in the germline of both Tetrahymena and C. elegans , may play a more direct role in repressing DSB formation by SPO-11 [28]. While the genome-wide distribution of this mark in C. elegans has not yet been reported, and nothing is yet known about its regulation, H3K23me3 has been found to be co-enriched on H3 tails that also carry H3K9me2 or H3K9me3 [29]. …”

Chromatin organization at the nuclear periphery as revealed by image analysis of structured illumination microscopy data

“…The presence of H3K23me2 in C. elegans has been shown to correlate with regions that have H3K9me3 and heterochromatic regions (Vandamme et al, 2015). However, information on mammalian cells is scarce.…”

“…Although the functions of many histone modifications have been elucidated, many still remain to be resolved. In general, the modifications H3K9me3, H2K9me, H3K27me2 and H3K27me3, as well as the recently described H3K23me2 (Vandamme et al, 2015), are associated with transcriptional silencing and formation of heterochromatin (Bannister and Kouzarides, 2011). The modifications associated with transcription activation are H3K4me3, H4K2me, H3K9Ac, H3K36me3 and H4K5Ac (Harr et al, 2016).…”