Our genome is packaged into chromatin, which allows cells to control the accessibility of all DNA encoded information. The selective incorporation of specialized histone proteins, or variants, into chromatin is an important feature of epigenetic regulation. A main focus of our lab is one such protein, the histone variant H3.3. The identification of mutations in H3.3 and associated proteins in human cancers and developmental disorders has heightened the need to understand the role of this histone variant in normal development and adult homeostasis.

How H3.3 contributes uniquely to chromatin function is a long-standing, unanswered question in the field. While long associated with gene activation, our recent studies establish that H3.3 also deposited at repetitive, heterochromatic regions of the genome, with deposition at each region facilitated by independent chaperone complexes.

The goals of this arm of our research program are to:

• Understand how H3.3 is partitioned between its two chaperone complexes

• Determine how H3.3 deposition influences local chromatin landscapes and downstream genome usage

• Discover new proteins that interact with H3.3 and their role in genome regulation

• Understand the functional role of H3.3 in both embryonic and adult stem cell models

Key Publications

H3.3 contributes to chromatin accessibility and transcription factor binding at promoter-proximal regulatory elements in embryonic stem cells
Tafessu A, O’Hara R, Martire S, Dube AL, Saha P, Gant VU, Banaszynski LA. (2023) Genome Biology, 24, 25. [paper]

ATRX promotes heterochromatin formation to protect cells from G-quadruplex DNA-mediated stress
Teng Y-C, Sundaresan A, O’Hara R, Gant VU, Li M, Martire S, Warshaw JN, Basu A, Banaszynski LA. (2021) Nature Communications 12, 3887. [paper]

Phosphorylation of histone H3.3 at serine 31 promotes p300 activity and enhancer acetylation
Martire S, Gogate AA, Whitmill A, Tafessu A, Nguyen J, Teng Y-C, Tastemel M, Banaszynski LA. (2019) Nature Genetics 51, 941-946. [paper]

Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells
Elsässer SJ*, Noh K-M, Diaz N, Allis CD, Banaszynski LA.* (2015) Nature 522, 240-244. *equal contribution [paper]

Hira-dependent histone H3.3 deposition facilitates PRC2 recruitment at developmental loci in ES cells
Banaszynski LA, Wen D, Dewell S, Whitcomb SJ, Lin M, Diaz N, Elsässer SJ, Chapgier A, Goldberg AD, Canaani E, Rafii S, Zheng D, Allis CD. (2013). Hira-dependent histone H3.3 deposition facilitates PRC2 recruitment at developmental loci in ES cells. Cell 155, 107-120. [paper]

Distinct factors control histone variant H3.3 localization at specific genomic regions
Goldberg AD, Banaszynski LA*, Noh K-M*, …, Allis CD. (2010) Cell 140, 678-691. *equal contribution [paper]

Literature Review

The roles of histone variants in fine-tuning chromatin organization and function
Martire S and Banaszynski LA. (2020) Nat. Rev. Mol. Cell Bio. 21, 522-541. [paper]