Sundeep Kalantry

Cells retain their identity by inheriting gene expression profiles of their predecessors. Patterns of transcription that survive cell division are established and maintained partly through covalent modifications of histones and DNA. Evidence increasingly implicates this epigenetic mode of inheritance in a myriad of developmental processes as well as a cause of or a significant contributor to human disease. We strive to elucidate principles of epigenetic inheritance through the study of X-chromosome inactivation, which is a paragon of epigenetic transcriptional regulation.

To gain insight into epigenetic inheritance, we investigate the process of X chromosome inactivation. X-inactivation 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.