Sperm-inherited H3K27me3 impacts offspring transcription and development in C. elegans

Abstract

Paternal epigenetic inheritance is gaining attention for its growing medical relevance. However, the form in which paternal epigenetic information is transmitted to offspring and how it influences offspring development remain poorly understood. Here we show that in C. elegans, sperm-inherited chromatin states transmitted to the primordial germ cells in offspring influence germline transcription and development. We show that sperm chromosomes inherited lacking the repressive histone modification H3K27me3 are maintained in that state by H3K36me3 antagonism. Inheritance of H3K27me3-lacking sperm chromosomes results in derepression in the germline of somatic genes, especially neuronal genes, predominantly from sperm-inherited alleles. This results in germ cells primed for losing their germ cell identity and adopting a neuronal fate. These data demonstrate that histone modifications are one mechanism through which epigenetic information from a father can shape offspring gene expression and development.

Trans-generational inheritance of centromere identity requires the CENP-A N-terminal tail in theC. elegansmaternal germ line

“…This form of inheritance has been reported previously in C. elegans , often for proteins that stabilize chromatin marks [75]. One example is the polycomb repressive complex 2 (PRC2), which maintains H3K27me3 during embryogenesis [76,77]. Recently, the H3.3 chaperone HIRA has also been implicated in setting a heritable chromatin state in the maternal germ line that can be maintained into adulthood [78].…”

Caenorhabditis elegans SET1/COMPASS Maintains Germline Identity by Preventing Transcriptional Deregulation Across Generations

“…Because active chromatin marks including H3K4me3 are mostly absent from the X chromosomes in proliferating and early meiotic germ cells (Kelly et al, 2002;Tabuchi et al, 2018;Han et al, 2019;Kaneshiro et al, 2019), loss of H3K4me3 in set-2 mutant germlines is unlikely to play a causal role on the X. Rather, loss of H3K4me3 may indirectly affect chromatin structure, and hence transcription on the X.…”

Targeted reprogramming of H3K27me3 resets epigenetic memory in plant paternal chromatin

“…Whether the bivalent marks detected on residual histones in mouse and human sperm directly impact transcription during early embryogenesis has been debated [43][44][45][46] . This is likely more plausible in species with histone-based sperm chromatin like zebrafish 47 and Caenorhabditis elegans 48 , with the latter requiring paternally-derived H3K27me3 for normal offspring development 49 . Our findings suggest that paternal resetting of H3K27me3 and inheritance of H3K4me3-primed genes has the potential to impact transcription after double fertilization in flowering plants, either directly or indirectly.…”