Pops gets the polycomb.

Abstract

The paternal and maternal chromosomes of the early embryo are molecularly distinct at a key region of DNA that forms pericentric heterochromatin. It is there that the male DNA is bound by Polycomb Repressive Complex 1 (PRC1) proteins, and the female DNA is not. A new study in mice provides a molecular framework for this difference [1]. In mice, pericentric heterochromatin is built by 234-basepair-long AT-rich satellite repeat sequences. The exact function of these regions is still being investigated, but they may help to organize the nucleus and possibly attract other DNA domains for transcriptional silencing. The maternal pericentric heterochromatin contains H3K9me3 marks, which are known to foster DNA silencing. These marks are assembled on maternal DNA during oogenesis and persist through fertilization. In males, this mark is absent from pericentric heterochromatin—instead, PRC1 has taken over the silencing function. Mathieu Tardat et al. now outline, in molecular detail, how PRC1 is supplied to paternal DNA but is excluded from maternal DNA. A central player in this mechanism is Cbx2, a component of PRC1. It seems that one domain of Cbx2 fosters binding to AT-rich satellite regions, and a separate domain fosters binding to a histone mark specifically enriched on paternal pericentric heterochromatin H3K27me3. This mark is deposited onto paternal DNA sometime after the replacement of protamines by histones. Cbx2 is thwarted from binding to maternal DNA by Hp1b, a protein that binds to the histone marks enriched at maternal pericentric heterochromatin H3K9me3. Eliminating Hp1b in zygotes results in PRC1 binding to the maternal pericentric heterochromatin. The researchers say that this mechanism probably also operates in chromosomal regions outside of pericentric heterochromatin—PRC1, for instance, is found in regions of the paternal chromosomal arms in the early embryo. The differences between the maternal and paternal pericentric heterochromatin begin to disappear at the 8-cell stage, and the researchers speculate that this shift may be necessary to foster zygotic transcription and cell fate specification. The findings also showcase how different reprogramming histories during sperm and oocyte development influence the localization and function of chromatin-binding proteins at maternal and paternal DNA in the early embryo.