Work

Evolutionary Adaptation of an HP1-protein Chromodomain Integrates Chromatin and DNA Sequence Signals

Year: 2024

Type: preprint

Abstract: Members of the diverse heterochromatin protein 1 (HP1) family play crucial roles in heterochromatin formation and maintenance. Despite the similar affinities of their chromodomains for di- and tri-methylated histone H3 lysine 9 (H3K9me2/3), different HP1 proteins exhibit distinct chromatin binding patterns, likely due to interactions with various specificity factors. Here, we elucidate the molecular basis of the interaction between the HP1 protein Rhino, a crucial factor of the Drosophila piRNA pathway, and Kipferl, a DNA sequence-specific C2H2 zinc finger protein and Rhino guidance factor. Through phylogenetic analyses, structure prediction, and in vivo genetics, we identify a single amino acid change within Rhino’s chromodomain, G31D, that does not affect H3K9me2/3 binding but disrupts the interaction between Rhino and Kipferl. Flies carrying the rhinoG31Dmutation phenocopy kipferl mutant flies, with Rhino redistributing from piRNA clusters to satellite repeats, causing pronounced changes in the ovarian piRNA profile of rhinoG31D flies. Thus, Rhino’s chromodomain functions as a dual-specificity module, facilitating interactions with both a histone mark and a DNA-binding protein.

Source: eLife

DOI: 10.7554/elife.93194.2