Barbara Panning, PhD


X chromosome inactivation is among the most fascinating examples of epigenetic regulation of gene expression. The transcriptional repression of one X chromosome in female somatic cells serves to equalize X-linked gene dosage between XX females and XY males. X-inactivation occurs early in mammalian development, upon transition of pluripotent embryonic cells to more developmentally restricted cell types. To achieve X-inactivation cells must be a mechanism that determines X chromosome number, restricting this process to cells with more than one X chromosome. The Xist gene plays a crucial role in initiating the X chromosome-wide alteration in chromatin structure and ensuring that is restricted to one of two otherwise equivalent X chromosomes. We study the molecular mechanisms by which Xist regulates X chromosome silencing.

The Xist gene is required in cis for X chromosome inactivation. Xist encodes an RNA of nearly 20 kb, which does not produce a protein. Early in development, Xist expression is upregulated on one X chromosome, the RNA speads in cis to cover the chromosome, and this triggers a series of changes in chromatin structure that mediated chromosome-wide silencing. Subsequently, Xist RNA continues to coat the inactive X in all daughter cells, where it plays a role in maintenance of transcriptional silencing. The work in my lab is aimed at understanding three fundamentally important aspects of X-inactivation. How does Xist RNA function to alter chromatin structure? How is Xist expression and X-inactivation coupled to differentiation of pluripotent embryonic cells? And, how does Xist regulate the random choice of a single X chromosome for silencing?