de novo H3.2K9me2 deposition pathway establishes heterochromatin for suppressing transposon mobilizations during somatic development [RNA-Seq]

Depleting the factors involving in the complex of DSC H3.2 chaperons, but not DNA synthesis-independent (DSI) H3.3 chaperons, led to the failure of heterochromatin formation, unleashing massive activation of retrotransposons. DSC chaperones specifically establish di-methylation at H3.2K9 site through directly interacting and recruiting histone methyltransferase, G9a, to heterochromatic regions. Intriguingly, we also discovered that the crosstalk of DSC H3.2K9me2 and DSI H3.3K9me3 in heterochromatin during development is dynamically regulated and properly balanced.

Although the DSI H3.3K9me3 could efficiently incorporate into transposon DNA when DSC H3.2K9me2 deposition pathway was compromised, H3.3K9me3 was still unable to establish functional heterochromatin to achieve transposon silencing during development. Collectively, our discoveries provide a framework to understand how cells employ deposition of specific histone modifications to establish and underpin heterochromatin states for silencing transposon mobilizations and safeguarding genome stability.