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METTL9 methylates H2B a-N-proline and suppresses human retrotransposition

ABSTRACT: The methylation of residues within histones plays a central role in regulating genome function; however, little is known about the biological importance of a-N-terminal histone methylation. Here we explored the function of the previously uncharacterized a-N methylation of mammalian histone 2B proline 1 (H2BP1me). Genome-wide analyses revealed an enrichment of H2BP1 methylation at certain transposable elements (TEs) and repetitive genomic sequences. We identified a novel histone methyltransferase, METTL9, which specifically methylates H2BP1. Depletion of METTL9 led to reduced H2BP1me2 levels, an accumulation of gH2A.X, expression activation of some TEs, and increased retrotransposition of a human LINE-1 containing a reporter gene; the latter being a unique feature amongst histone modifiers described to date. These data suggest that reduced H2BP1 methylation may lead to increased TE activity and genome instability. Indeed, decreased levels of H2BP1 methylation in colon tumors correlated with an increase in LINE-1 protein expression. Furthermore, METTL9 depletion in cultured cells led to an enhancement of cellular proliferation, invasion, and migration, suggesting that a loss of H2BP1 methylation could play a role in cancer progression. Thus, we have identified a new role for H2BP1 N-terminal histone methylation in regulating chromatin function and perhaps disease progression, thereby highlighting the role of METTL9 as a novel guardian of genomic stability.

ORGANISM(S): Homo sapiens

PROVIDER: GSE60176 | GEO | 2018/12/02

REPOSITORIES: GEO

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