Premium
KMT 1 family methyltransferases regulate heterochromatin–nuclear periphery tethering via histone and non‐histone protein methylation
Author(s) -
Rao Radhika Arasala,
Ketkar Alhad Ashok,
Kedia Neelam,
Krishnamoorthy Vignesh K,
Lakshmanan Vairavan,
Kumar Pankaj,
Mohanty Abhishek,
Kumar Shilpa Dilip,
Raja Sufi O,
Gulyani Akash,
Chaturvedi Chandra Prakash,
Brand Marjorie,
Palakodeti Dasaradhi,
Rampalli Shravanti
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201643260
Subject(s) - heterochromatin , histone methyltransferase , heterochromatin protein 1 , ezh2 , euchromatin , histone methylation , biology , methyltransferase , histone , methylation , microbiology and biotechnology , dna methylation , genetics , chromatin , gene expression , dna , gene
Euchromatic histone methyltransferases ( EHMT s), members of the KMT 1 family, methylate histone and non‐histone proteins. Here, we uncover a novel role for EHMT s in regulating heterochromatin anchorage to the nuclear periphery ( NP ) via non‐histone methylation. We show that EHMT s methylate and stabilize LaminB1 ( LMNB 1), which associates with the H3K9me2‐marked peripheral heterochromatin. Loss of LMNB 1 methylation or EHMT s abrogates heterochromatin anchorage at the NP . We further demonstrate that the loss of EHMT s induces many hallmarks of aging including global reduction of H3K27methyl marks and altered nuclear morphology. Consistent with this, we observe a gradual depletion of EHMT s, which correlates with loss of methylated LMNB 1 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 EHMT s regulate heterochromatin domain organization and reveals their impact on fundamental changes associated with the intrinsic aging process.