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, and do not involve changes in the DNA sequence itself.  Emerging 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.  Our research strives to further the understanding of epigenetic mechanisms through the study of X-chromosome inactivation.  X-inactivation is an instrument of dosage compensation that equalizes X-linked gene expression between XY male and XX female mammals, via transcriptional silencing of one of the two X-chromosomes in early female embryos.  Once enacted in individual cells, X-inactivation is stably transmitted such that all descendant cells maintain silencing of that X-chromosome.  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 and are being found to be important in cell fate decisions during embryogenesis, in stem cell biology, and during disease progression.  While many forms of epigenetic modifications of chromatin correlate with silenced gene expression, those that trigger gene silencing remain elusive.  The identification of factors and mechanisms that bring about heritable changes in gene expression is the focus of our research.