SetDB1 and Su(var)3-9 play non-overlapping roles in somatic cell chromosomes of Drosophila melanogaster

Abstract

We explored functional roles of two H3K9-specific histone methyltransferases SetDB1 and Su(var)3-9. Using DamID approach, we generated the binding profile for SetDB1 in Drosophila salivary gland chromosomes, and matched it to the profile of Su(var)3-9. Unlike Su(var)3-9, SetDB1 turned out to be an euchromatic protein that is absent from repeated DNA compartment, and is largely restricted to TSSes and 5'UTRs of ubiquitously expressed genes. Significant SetDB1 association is also observed at insulator protein CP190 binding sites. SetDB1 and H3K9me2/3-enriched sites tend to display poor overlap. At the same time, SetDB1 has clear connection with the distribution of H3K27me3 mark. SetDB1 binds outside the domains possessing this modification, and about half of the borders of H3K27me3 domains are decorated by SetDB1 together with actively transcribed genes. On the basis of poor correlation between the distribution of SetDB1 and H3K9 methylation marks, we speculate that in somatic cells, SetDB1 may contribute to the methylation of a broader set of chromosomal proteins than just H3K9. In addition, SetDB1 can be expected to play a role in the establishment of chromatin functional domains.