Regulated nuclear accumulation of a histone methyltransferase times the onset of heterochromatin formation in C. elegans embryos

Beste Mutlu, Huei Mei Chen, James J. Moresco, Barbara D. Orelo, Bing Yang, John M. Gaspar, Sabine Keppler-Ross, John R. Yates, David H. Hall, Eleanor M. Maine, Susan E. Mango

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Heterochromatin formation during early embryogenesis is timed precisely, but how this process is regulated remains elusive. We report the discovery of a histone methyltransferase complex whose nuclear accumulation and activation establish the onset of heterochromatin formation in Caenorhabditis elegans embryos. We find that the inception of heterochromatin generation coincides with the accumulation of the histone H3 lysine 9 (H3K9) methyltransferase MET-2 (SETDB) into nuclear hubs. The absence of MET-2 results in delayed and disturbed heterochromatin formation, whereas accelerated nuclear localization of the methyltransferase leads to precocious H3K9 methylation. We identify two factors that bind to and function with MET-2: LIN-65, which resembles activating transcription factor 7–interacting protein (ATF7IP) and localizes MET-2 into nuclear hubs, and ARLE-14, which is orthologous to adenosine 5′-diphosphate–ribosylation factor-like 14 effector protein (ARL14EP) and promotes stable association of MET-2 with chromatin. These data reveal that nuclear accumulation of MET-2 in conjunction with LIN-65 and ARLE-14 regulates timing of heterochromatin domains during embryogenesis.

Original languageEnglish (US)
Article numbereaat6224
JournalScience Advances
Volume4
Issue number8
DOIs
StatePublished - Aug 22 2018

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Regulated nuclear accumulation of a histone methyltransferase times the onset of heterochromatin formation in C. elegans embryos'. Together they form a unique fingerprint.

Cite this