Department of Biotechnology
inStem (Institute for Stem Cell Science and Regenerative Medicine)

KMT1 family methyltransferases regulate heterochromatin-nuclear periphery tethering via histone and non-histone protein methylation.

Publication Type

Research Support, Non-U.S. Gov't

Date of Publication

May 1, 2019

Journal

EMBO reports

Volume/Issue

20/5

ISSN

1469-3178

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.

Alternate Journal

EMBO Rep

PubMed ID

30858340

PubMed Central ID

PMC6501005

Authors

Radhika Arasala Rao
Alhad Ashok Ketkar
Neelam Kedia
Vignesh K Krishnamoorthy
Vairavan Lakshmanan
Pankaj Kumar
Abhishek Mohanty
Shilpa Dilip Kumar
Sufi O Raja
Akash Gulyani
Chandra Prakash Chaturvedi
Marjorie Brand
Dasaradhi Palakodeti
Shravanti Rampalli

Keywords

Methylation
Histones
Aging
Cell Nucleus
Heterochromatin
Lamin Type B
Humans
HEK293 Cells
Cell Line
Histone-Lysine N-Methyltransferase