Differential binding of EHMT1,H3k9me2,LMNB1 in fetal Vs adult fibroblast. Homo sapiens

Perinuclear heterochromatin is an emerging nuclear domain for driving many normal and disease processes, including development, cancer and aging. Here we uncover a novel role for Euchromatic histone methyltransferases 1 in tethering heterochromatin to the nuclear periphery (NP). Surprisingly, depletion of EHMT1 was sufficient to release heterochromatin from the periphery. In search for the mechanism, we identified that the EHMT1 regulates factors critical for heterochromatin organization and stability of laminB1 via its methylation, thereby regulating higher order chromatin organization at the NP. Loss of EHMT1 induced many hallmarks of aging including global reduction of H3K27me2/3 marks along with altered nuclear morphology. Keeping consistent with this, we observed gradual loss of EHMT1 and methylated LMNB1 in aging human fibroblasts. Collectively our studies elucidated a new mechanism by which EHMT1 regulate heterochromatin domain organization and explains its impact on fundamental changes associated with the intrinsic aging process.