Pluto Bioinformatics

GSE102688: Structural and mechanistic insights into ATRX-dependent and independent functions of the histone chaperone DAXX [RNA-seq]

Bulk RNA sequencing

The histone variant H3.3 is incorporated in a replication-independent manner at heterochromatic regions by the ATRX-DAXX histone chaperone complex. Here, we present a high-resolution x-ray crystal structure of an interaction surface between ATRX and DAXX. We used single amino acid substitutions in DAXX that abrogate formation of the complex to explore ATRX-dependent and -independent functions of DAXX. We found that the repression of specific murine endogenous retroviruses is dependent on DAXX, but not on ATRX. In support, we reveal the existence of two biochemically distinct DAXX-containing complexes: The ATRX-DAXX complex involved in gene repression and telomere chromatin structure, and a DAXX-SETDB1-KAP1-HDAC1 complex that represses endogenous retroviruses independently of ATRX and H3.3 incorporation into chromatin. We found that histone H3.3 stabilizes DAXX protein levels and affects DAXX-regulated genes independently of its incorporation into nucleosomes. Our findings represent the first description of a nucleosome-independent function for the H3.3 histone variant. SOURCE: Peter,W,Lewis (pwlewis2@wisc.edu) - Department of Biomolecular Chemistry University of Wisconsin-Madison