RT Journal Article
SR Electronic
T1 Regulated nuclear accumulation of a histone methyltransferase times the onset of heterochromatin formation in <em>C. elegans</em> embryos
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 326231
DO 10.1101/326231
A1 Beste Mutlu
A1 Huei-Mei Chen
A1 James J. Moresco
A1 Barbara D. Orelo
A1 Bing Yang
A1 John M. Gaspar
A1 Sabine Keppler-Ross
A1 John R. Yates III
A1 David H. Hall
A1 Eleanor M. Maine
A1 Susan E. Mango
YR 2018
UL http://biorxiv.org/content/early/2018/05/18/326231.abstract
AB Heterochromatin formation during early embryogenesis is timed precisely, but it has been elusive how this process is regulated. Here we report the discovery of a histone methyltransferase complex whose nuclear accumulation and activation establishes the onset of heterochromatin formation in C. 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 ATF7IP, localizes MET-2 into nuclear hubs, and ARLE-14, orthologous to ARL14EP, 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.ONE SENTENCE SUMMARY: MET-2/SETDB1 and interactors LIN-65/ATF7IP and ARLE-14/ARL14EP initiate heterochromatin formation during embryogenesis.