PT  - JOURNAL ARTICLE
AU  - Alhad Ashok Ketkar
AU  - Radhika Arasala Rao
AU  - Neelam Kedia
AU  - Febina Ravindran
AU  - Vairavan Lakshmanan
AU  - Pankaj Kumar
AU  - Abhishek Mohanty
AU  - Shilpa Dilip Kumar
AU  - Sufi O Raja
AU  - Akash Gulyani
AU  - ChandraPrakash Chaturvedi
AU  - Marjorie Brand
AU  - Dasaradhi Palakodeti
AU  - Shravanti Rampalli
TI  - Euchromatic histone methyltransferases regulate peripheral heterochromatin tethering via histone and non-histone protein methylations
AID  - 10.1101/240952
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 240952
4099  - http://biorxiv.org/content/early/2018/01/02/240952.short
4100  - http://biorxiv.org/content/early/2018/01/02/240952.full
AB  - Euchromatic histone methyltransferases (EHMTs) methylate histone and non-histone proteins. Here we uncover a novel role for Euchromatic histone methyltransferases in regulating heterochromatin anchorage to the nuclear periphery (NP) via non-histone (LMNB1) methylations. In search for mechanism, we identified EHMTs methylate LMNB1 that associates with the H3K9me2 marked peripheral heterochromatin. Loss of LMNB1 methylation or EHMTs abrogates the heterochromatin anchorage from the nuclear periphery. We further demonstrate that the loss of EHMTs induced many hallmarks of aging including global reduction of H3K27methyl marks along with altered nuclear-morphology. Keeping consistent with this, we observed gradual depletion of EHMTs, which correlated with loss of methylated LaminB1 and peripheral heterochromatin in aging human fibroblasts. Restoration of EHMT expression reverts peripheral heterochromatin defect in aged cells. Collectively our studies elucidated a new mechanism by which EHMTs regulate heterochromatin domain organization and explains its impact on fundamental changes associated with the intrinsic aging process.