X-chromosome inactivation is an instrument of dosage compensation that equalizes X-linked gene expression between male and female mammals, via transcriptional silencing of one of the two X-chromosomes in early female embryos. Once inactivated, with a few key exceptions, replicated copies of the inactive X-chromosome are maintained stably as inactive in descendant cells.
Since an entire chromosome is inactivated and therefore readily detected, X-inactivation is a model system to investigate transcriptional memory mechanisms. Importantly, the memory mechanisms that operate during X-inactivation also apply broadly to gene regulation elsewhere in the genome and are important in cell fate decisions during embryogenesis, in stem cell biology, and during disease progression. While many chromatin modifications correlate with silenced gene expression, those that cause epigenetic transcriptional silencing remain elusive. The identification of factors and mechanisms that execute heritable changes in gene expression is the focus of our research.
The links below provide a snapshot of some of our projects: