Invited Speaker Australian Epigenetics Alliance Conference 2022

Eight principal chromatin states separate the genome into developmental and housekeeping roles in Drosophila melanogaster (#3)

Owen Marshall 1
  1. Menzies Institute for Medical Research, Hobart, TAS, Australia

Chromatin states in Drosophila have been profiled by multiple groups over the last decade. Surprisingly, these studies do not agree on the fundamental organisation of chromatin, with protein-based DamID studies identifying very different active forms of chromatin to histone-mark ChIP-seq studies. While DamID studies have identified developmental states associated with Trithorax-group (TrxG) complexes and house-keeping states associated with MRG15, ChIP-seq modelling has focussed upon gene transcriptional elements that do not separate by gene ontology.

Here, combining DamID, ChIP-seq, RNA-seq and 3D genome datasets across multiple cell types, we unify protein and histone-mark data and demonstrate that fly chromatin is organised into eight principle chromatin types. We show that active states are divided by a refractory relationship between the Swi/Snf chromatin remodelling complex and MRG15/H3K36me3 into a Swi/Snf state associated with developmental genes, and a Yellow state associated with housekeeping and metabolic genes. We demonstrate the existence of a previously-undocumented form of chromatin that silences housekeeping and metabolic genes cell-type specifically. We show that the Black chromatin silent state of DamID studies, associated with Histone H1 and Lamin enrichment, is directly equivalent to the “low signal” states of ChIP-seq data, and represses the majority of developmental genes in non-terminally-differentiated cell types.

We show that through eight chromatin states, the genome is fundamentally divided along developmental and housekeeping/metabolic lines, and that this division covers not only gene bodies but enhancers, core promoters and regulatory transcription factor motifs. Our results suggest a more complex organisation of the chromatin landscape than has been previously recognised and show that at every level the genome is divided by gene function along developmental and housekeeping/metabolic roles.