Abstract:
: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.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Rao RA,Ketkar AA,Kedia N,Krishnamoorthy VK,Lakshmanan V,Kumar P,Mohanty A,Kumar SD,Raja SO,Gulyani A,Chaturvedi CP,Brand M,Palakodeti D,Rampalli Sdoi
10.15252/embr.201643260subject
Has Abstractpub_date
2019-05-01 00:00:00issue
5eissn
1469-221Xissn
1469-3178pii
embr.201643260journal_volume
20pub_type
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