TY - JOUR T1 - KMT1 family methyltransferases regulate heterochromatin-nuclear periphery tethering via histone and non-histone protein methylation. JF - EMBO Rep Y1 - 2019 A1 - Rao, Radhika Arasala A1 - Ketkar, Alhad Ashok A1 - Kedia, Neelam A1 - Krishnamoorthy, Vignesh K A1 - Lakshmanan, Vairavan A1 - Kumar, Pankaj A1 - Mohanty, Abhishek A1 - Kumar, Shilpa Dilip A1 - Raja, Sufi O A1 - Gulyani, Akash A1 - Chaturvedi, Chandra Prakash A1 - Brand, Marjorie A1 - Palakodeti, Dasaradhi A1 - Rampalli, Shravanti AB -

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.

ER -