H3.3 and gene activation
We use mouse embryonic stem cells to study how H3.3 incorporation influences chromatin at regulatory elements, with downstream consequences for gene expression. We are particularly interested in how this mechanism of gene regulation might influence cell fate decisions during differentiation and development.
Chromatin regulation of repetitive DNA
In addition to genes, our recent studies have shown that H3.3 is enriched at repetitive regions such as telomeres and endogenous retroelements. Deposition at these regions is mediated by the ATRX/DAXX complex. This complex is mutated in many human cancers, with links to a process known as alternative lengthening of telomeres, or ALT. We study mechanisms that regulate this deposition pathway, in the hopes of gaining insights into how misregulation can lead to cancer.
Our long-term goal is to determine how chromatin influences developmental cell-fate decisions. We take the view that chromatin acts as both a platform for the integration of signaling information received from local cellular environments, as well as a regulator of gene expression changes required for cellular response to these signals. We are interested in how this interplay allows cells to alter their identity, both in the context of development and disease.