Trans-generational epigenetic regulation of C. elegans primordial germ cells

Abstract

BackgroundThe processes through which the germline maintains its continuity across generations has long been the focus of biological research. Recent studies have suggested that germline continuity can involve epigenetic regulation, including regulation of histone modifications. However, it is not clear how histone modifications generated in one generation can influence the transcription program and development of germ cells of the next.ResultsWe show that the histone H3K36 methyltransferase maternal effect sterile (MES)-4 is an epigenetic modifier that prevents aberrant transcription activity in Caenorhabditis elegans primordial germ cells (PGCs). In mes-4 mutant PGCs, RNA Pol II activation is abnormally regulated and the PGCs degenerate. Genetic and genomewide analyses of MES-4-mediated H3K36 methylation suggest that MES-4 activity can operate independently of ongoing transcription, and may be predominantly responsible for maintenance methylation of H3K36 in germline-expressed loci.ConclusionsOur data suggest a model in which MES-4 helps to maintain an 'epigenetic memory' of transcription that occurred in germ cells of previous generations, and that MES-4 and its epigenetic product are essential for normal germ cell development.

RNA Polymerase II transcription elongation and Pol II CTD Ser2 phosphorylation

“…In contrast to its essential role in somatic Ser2-P, CDK-9 is not required for the bulk of Ser2 phosphorylation in the germline, which instead requires CDK-12. 59,169 While it is unexpected that C. elegans germline Ser2-P does not require CDK-9, this pattern of Ser2-P regulation is surprisingly similar to that seen in yeast (Fig. 1A).…”

Broad chromosomal domains of histone modification patterns in C. elegans

“…But surprisingly, the active mark H3K36me3 is significantly higher on germline-specific genes than soma-specific genes. As noted above, in-depth comparative analysis has revealed that H3K36me3 marks are propagated on germline-specific genes by the MES-4 histone methyltransferase in the absence of ongoing transcription (Furuhashi et al 2010;Rechtsteiner et al 2010). Consistent with the notion that germlinespecific genes retain at least one mark of active chromatin (H3K36me3) in early embryos, these genes have very low levels of the repressive mark H3K27me3.…”

“…MES-4, which can catalyze H3K36 methylation independently of RNA Pol II, associates preferentially with autosomal genes (Bender et al 2006;Rechtsteiner et al 2010). MET-1, which is presumed to depend on RNA Pol II like other H3K36 histone methyltransferases, can methylate genes on the X but is present at low levels in early embryos (Furuhashi et al 2010;Rechtsteiner et al 2010). The elevated H3K36me3 on highly expressed autosomal genes in L3s has not been similarly investigated, but may also be due to the autosome-concentrated activity of MES-4.…”

“…These studies showed that the organization of C. elegans genic chromatin has properties similar to those of other organisms and additionally provided novel insights into chromatin structure and function (Whittle et al 2008;Gu and Fire 2009;Kolasinska-Zwierz et al 2009;Ooi et al 2009;Furuhashi et al 2010;Greer et al 2010;Hall et al 2010;Rechtsteiner et al 2010). For example, H3K4me3 and the histone variant HTZ-1/H2A.Z were found to be enriched in promoter regions of actively transcribed genes and H3K36me3 on gene bodies, with the latter more enriched on exons than introns and transmitted during embryogenesis independently of ongoing transcription (Whittle et al 2008;Kolasinska-Zwierz et al 2009;Furuhashi et al 2010;Rechtsteiner et al 2010). Further studies of H3K4me3 uncovered links with longevity and developmental life history (Greer et al 2010;Hall et al 2010).…”

Genes for embryo development are packaged in blocks of multivalent chromatin in zebrafish sperm

“…Two studies have recently shown the deposition of H3K36me in a transcription-independent manner in the germline of C. elegans (Furuhashi et al 2010;Rechtsteiner et al 2010).…”