Histones are central to how genomes are organized and regulated, but whether they act as true carriers of epigenetic information remains a fundamental and unresolved question in biology.

Our work aims to directly test how histone proteins and their chemical modifications contribute to the establishment, maintenance, and inheritance of gene expression states during development.

Central hypothesis:  we test the hypothesis that specific histone modifications actively encode epigenetic information, rather than merely reflecting transcriptional states.

A Unique Experimental System
A major focus of our studies is the development of engineered histone gene clusters in Drosophila. This system allows precise, in vivo manipulation of histone proteins and their post-translational modifications, thereby enabling direct tests of epigenetic mechanisms in multicellular animals.

Recent Discoveries
Recent work from our lab demonstrates that specific histone modifications (including H3K4, H3K9, and H3K27) play critical and sometimes unexpected roles in regulating gene expression programs and maintaining cell identity.

Using engineered histone gene replacement systems, we have begun to test long-standing models of epigenetic gene regulation in animals. Our most recent histone replacement platform is the most versatile system yet, enabling experimental approaches that were previously out of reach.

Histone post-translational modifications are highly correlated with gene expression states, but their roles in gene regulation have largely been inferred. Through histone gene replacement systems, we test the consequences of directly mutating the histones themselves.

Questions we ask:

• Which histone residues contribute to transcriptional regulation?
• Do histone PTM writer mutant phenotypes match those of mutant histone residues?  If not, why?
• How do histone PTMs contribute to initiation and maintenance of cellular identity?
• Do histone PTMs control 3D genome organization?