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

6 Citations (Scopus)

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

Fingerprint

Heterochromatin
Embryonic Structures
Embryonic Development
Activating Transcription Factors
Caenorhabditis elegans
Methyltransferases
Histones
Adenosine
Methylation
Lysine
Chromatin
Proteins
histone methyltransferase

ASJC Scopus subject areas

  • General

Cite this

Mutlu, B., Chen, H. M., Moresco, J. J., Orelo, B. D., Yang, B., Gaspar, J. M., ... Mango, S. E. (2018). Regulated nuclear accumulation of a histone methyltransferase times the onset of heterochromatin formation in C. elegans embryos. Science advances, 4(8), [eaat6224]. https://doi.org/10.1126/sciadv.aat6224

Regulated nuclear accumulation of a histone methyltransferase times the onset of heterochromatin formation in C. elegans embryos. / Mutlu, Beste; Chen, Huei Mei; Moresco, James J.; Orelo, Barbara D.; Yang, Bing; Gaspar, John M.; Keppler-Ross, Sabine; Yates, John R.; Hall, David H.; Maine, Eleanor M; Mango, Susan E.

In: Science advances, Vol. 4, No. 8, eaat6224, 22.08.2018.

Research output: Contribution to journalArticle

Mutlu, B, Chen, HM, Moresco, JJ, Orelo, BD, Yang, B, Gaspar, JM, Keppler-Ross, S, Yates, JR, Hall, DH, Maine, EM & Mango, SE 2018, 'Regulated nuclear accumulation of a histone methyltransferase times the onset of heterochromatin formation in C. elegans embryos', Science advances, vol. 4, no. 8, eaat6224. https://doi.org/10.1126/sciadv.aat6224
Mutlu, Beste ; Chen, Huei Mei ; Moresco, James J. ; Orelo, Barbara D. ; Yang, Bing ; Gaspar, John M. ; Keppler-Ross, Sabine ; Yates, John R. ; Hall, David H. ; Maine, Eleanor M ; Mango, Susan E. / Regulated nuclear accumulation of a histone methyltransferase times the onset of heterochromatin formation in C. elegans embryos. In: Science advances. 2018 ; Vol. 4, No. 8.
@article{0f79231849dc4f66be139c7803d2c741,
title = "Regulated nuclear accumulation of a histone methyltransferase times the onset of heterochromatin formation in C. elegans embryos",
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.",
author = "Beste Mutlu and Chen, {Huei Mei} and Moresco, {James J.} and Orelo, {Barbara D.} and Bing Yang and Gaspar, {John M.} and Sabine Keppler-Ross and Yates, {John R.} and Hall, {David H.} and Maine, {Eleanor M} and Mango, {Susan E.}",
year = "2018",
month = "8",
day = "22",
doi = "10.1126/sciadv.aat6224",
language = "English (US)",
volume = "4",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "8",

}

TY - JOUR

T1 - Regulated nuclear accumulation of a histone methyltransferase times the onset of heterochromatin formation in C. elegans embryos

AU - Mutlu, Beste

AU - Chen, Huei Mei

AU - Moresco, James J.

AU - Orelo, Barbara D.

AU - Yang, Bing

AU - Gaspar, John M.

AU - Keppler-Ross, Sabine

AU - Yates, John R.

AU - Hall, David H.

AU - Maine, Eleanor M

AU - Mango, Susan E.

PY - 2018/8/22

Y1 - 2018/8/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85052215774&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052215774&partnerID=8YFLogxK

U2 - 10.1126/sciadv.aat6224

DO - 10.1126/sciadv.aat6224

M3 - Article

C2 - 30140741

AN - SCOPUS:85052215774

VL - 4

JO - Science advances

JF - Science advances

SN - 2375-2548

IS - 8

M1 - eaat6224

ER -