Investigation of the Genome-Wide Distribution of Histone Variant H3.3

Abstract

Epigenetic regulation via loci-specific deposition of variant histone proteins is important for genome stability and regulation of gene expression. Replication-independent histone variant H3.3 has been implicated in epigenetic memory of cell states under normal physiological conditions and in tumorigenesis when improperly regulated. Multiple factors are responsible for H3.3 deposition in distinct genomic loci. Histone chaperone HIRA is known to deposit H3.3 at actively transcribed genes whereas H3.3 is deposited at heterochromatic loci by the ATRX-DAXX complex. Here we employ a quantitative high-throughput sequencing based approach in different genetic backgrounds to determine the genome-wide distribution of H3.3. We aim to characterize H3.3 enriched genomic loci as dependent on or independent from its known assembly factors - HIRA and DAXX. We also explore the mechanism by which H3.3 is being deposited into the genome and the possibility that a novel chaperone may be contributing to its deposition.