Affiliation:
1. Howard Hughes Medical Institute, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Abstract
DNA sequence and inherited gene silencing
Cell fate decisions require a gene's transcriptional status, whether on or off, to be stably and heritably maintained over multiple cell generations. For silenced genes, heterochromatin domains are associated with specific histone posttranslational modifications, and these histone marks are maintained during DNA replication and chromosome duplication (see the Perspective by De and Kassis). Laprell
et al.
show that parental methylated histone H3 lysine 27 (H3K27) nucleosomes in
Drosophila
are inherited in daughter cells after replication and can repress transcription, but that they are not sufficient to propagate the mark. Trimethylation of newly incorporated nucleosomes requires recruitment of the methyltransferase Polycomb repressive complex 2 (PRC2) to neighboring cis-regulatory DNA elements. Coleman and Struhl demonstrate that H3K27 trimethylated nucleosomes play a causal role in transmitting epigenetic memory at a
Drosophila
HOX gene through anchoring of PRC2 at the Polycomb response element binding site. Wang and Moazed examine fission yeast and show that both sequence-dependent and chromodomain sequence-independent mechanisms are required for stable epigenetic inheritance of histone modifications and the epigenetic maintenance of silencing. These studies highlight the crucial role of DNA binding for heritable gene silencing during growth and development.
Science
, this issue p.
85
, p.
eaai8236
, p.
88
; see also p.
28
Funder
National Institutes of Health
Howard Hughes Medical Institute
Publisher
American Association for the Advancement of Science (AAAS)
Cited by
105 articles.
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