De novo H3.2K9me2 deposition pathway establishes heterochromatin for suppressing transposon mobilizations during somatic development [Nanopore]

ABSTRACT: Histone variants along with their associated chaperons have been considered as one of the major complexes to provide versatility in organizing chromatin structure, contributing to define dynamic landscapes and maintaining genome integrity. Post translational modifications (PTMs) of H3 variants serves as very important factors in promoting heterochromatin assembly, protecting telomere stability and suppressing transposon activity. However, the precise mechanism regarding the specific PTMs of H3 variants in performing the function of heterochromatin formation and transposon silencing during somatic development remains elusive. Here, by monitoring retrotransposon activity and mobilizations during somatic development, we found that DNA synthesis-coupled (DSC) H3.2K9me2 deposition pathway plays a pivotal role in heterochromatin establishment and transposon suppression. 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.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE297693 | GEO | 2026/03/11

REPOSITORIES: GEO