KMT1 family methyltransferases regulate heterochromatin-nuclear periphery tethering via histone and non-histone protein methylation.
LaminB1
aging
euchromatic histone methyltransferases
heterochromatin
nuclear periphery
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
24
08
2016
revised:
07
02
2019
accepted:
12
02
2019
pubmed:
13
3
2019
medline:
1
5
2020
entrez:
13
3
2019
Statut:
ppublish
Résumé
Euchromatic histone methyltransferases (EHMTs), members of the KMT1 family, methylate histone and non-histone proteins. Here, we uncover a novel role for EHMTs in regulating heterochromatin anchorage to the nuclear periphery (NP) via non-histone methylation. We show that EHMTs methylate and stabilize LaminB1 (LMNB1), which associates with the H3K9me2-marked peripheral heterochromatin. Loss of LMNB1 methylation or EHMTs abrogates heterochromatin anchorage at the NP We further demonstrate that the loss of EHMTs induces many hallmarks of aging including global reduction of H3K27methyl marks and altered nuclear morphology. Consistent with this, we observe a gradual depletion of EHMTs, which correlates with loss of methylated LMNB1 and peripheral heterochromatin in aging human fibroblasts. Restoration of EHMT expression reverts peripheral heterochromatin defects in aged cells. Collectively, our work elucidates a new mechanism by which EHMTs regulate heterochromatin domain organization and reveals their impact on fundamental changes associated with the intrinsic aging process.
Identifiants
pubmed: 30858340
pii: embr.201643260
doi: 10.15252/embr.201643260
pmc: PMC6501005
pii:
doi:
Substances chimiques
Heterochromatin
0
Histones
0
Lamin Type B
0
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : DBT-Wellcome Trust India Alliance
ID : 500220-Z-11-Z
Pays : India
Organisme : DBT-Wellcome Trust India Alliance
ID : IA/I/16/1/502374
Pays : India
Informations de copyright
© 2019 The Authors. Published under the terms of the CC BY 4.0 license.
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