A Conserved Chromatin Architecture Marks and Maintains the Restricted Germ Cell Lineage in Worms and Flies

Abstract

In C. elegans, mRNA production is initially repressed in the embryonic germline by a protein unique to C. elegans germ cells, PIE-1. PIE-1 is degraded upon the birth of the germ cell precursors, Z2 and Z3. We have identified a chromatin-based mechanism that succeeds PIE-1 repression in these cells. A subset of nucleosomal histone modifications, methylated lysine 4 on histone H3 (H3meK4) and acetylated lysine 8 on histone H4 (H4acetylK8), are globally lost and the DNA appears more condensed. This coincides with PIE-1 degradation and requires that germline identity is not disrupted. Drosophila pole cell chromatin also lacks H3meK4, indicating that a unique chromatin architecture is a conserved feature of embryonic germ cells. Regulation of the germline-specific chromatin architecture requires functional nanos activity in both organisms. These results indicate that genome-wide repression via a nanos-regulated, germ cell-specific chromatin organization is a conserved feature of germline maintenance during embryogenesis.

Genetics of germ cell development

“…In D. melanogaster and C. elegans, repressive chromatin configurations take over from PIE-1 or Pgc-based global transcriptional inhibition around the time of gastrulation, when PIE-1 or Pgc protein levels decline. 45 The chromatin of the C. elegans germline founder cells, Z2 and Z3, is more condensed than that of the surrounding somatic cells. Z2 and Z3 have lower levels of the activating histone modifications di-and tri-methyl lysine 4 on histone H3 (H3K4me2 and H3K4me3) and acetylated lysine 8 on histone H4 (H4K8ac), and slightly higher levels of the repressive modification trimethyl lysine 27 on histone H3 (H3K27me3).…”

“…Z2 and Z3 have lower levels of the activating histone modifications di-and tri-methyl lysine 4 on histone H3 (H3K4me2 and H3K4me3) and acetylated lysine 8 on histone H4 (H4K8ac), and slightly higher levels of the repressive modification trimethyl lysine 27 on histone H3 (H3K27me3). 45,46 A complex of maternaleffect proteins including the POLYCOMB group orthologs MES-2 and MES-6 is required for deposition of the repressive H3K27me3 mark in germ cells; individuals lacking any of these complex components have offspring that fail to develop a germline. [46][47][48] Likewise, loss of the LSD1 histone demethylase homolog spr-5 results in progressive failure to demethylate H3K4, impaired transcriptional repression, and cumulative sterility over multiple generations, while absence of the nanos homologs nos-1 and nos-2 causes premature reaccumulation of H3K4me2/3 in the embryonic germline and corresponding germline failure and sterility.…”

“…[46][47][48] Likewise, loss of the LSD1 histone demethylase homolog spr-5 results in progressive failure to demethylate H3K4, impaired transcriptional repression, and cumulative sterility over multiple generations, while absence of the nanos homologs nos-1 and nos-2 causes premature reaccumulation of H3K4me2/3 in the embryonic germline and corresponding germline failure and sterility. 45,49 In D. melanogaster, germ cell precursors lacking nanos or the spr-5/LSD1…”

“…45,50 In mice, invocation of a repressive chromatin configuration is among the earliest events in the germ cell lineage. PRDM1, the early PGC marker, is required for repression of somatic developmental regulators.…”

A twist of fate: How a meiotic protein is providing new perspectives on germ cell development

“…Global transcriptional quiescence in Z2 and Z3 is maintained by epigenetic reprogramming of the PGCs, leading to loss of the active histone mark H3K4me2 and acquisition of a condensed chromatin state. 7 During this stage, zygotic expression initiates for a handful of germline genes that play key roles in germ cell differentiation, including transcripts for Pgranules components (pgl-1) and the nanos ortholog, nos-1. 8,9 Zygotic gene activation and resumption of the cell cycle occurs post-hatching in response to feeding.…”