Our long-term goal is to define the molecular mechanism of X chromosome inactivation, and through this to discover fundamental processes governing developmental gene regulation
Prof Neil Brockdorff
The Molecular Mechanism of X chromosome inactivation
X chromosome inactivation (X-inactivation) evolved in mammals to equalise gene expression levels in XX females relative to XY males. Briefly, cells of early female embryos co-ordinately silence most of the genes on one of their two X chromosomes. Once established X-inactivation is highly stable and is propagated through subsequent cell divisions, a classical example of epigenetic gene regulation.
Our long-term goal is to define the molecular mechanism of X-inactivation, and through this to discover fundamental processes governing developmental gene regulation. In early studies we discovered that a specialised RNA molecule, Xist, acts as the key regulator of X-inactivation. Xist RNA is transcribed from and then accumulates over the chromosome that is to be inactivated, triggering the recruitment of factors that modify underlying chromatin. We are working towards identifying the key interacting factors and their mode of action in chromosome silencing.
Our ongoing studies take us from embryology and genetics, through to cell biology, molecular biology, biochemistry and biophysics. Key methodologies include genome/proteome engineering, super-resolution, live-cell and ultrastructural imaging, and high-throughput sequencing based methods (RNA-seq, ChIP-seq, etc).
To find out more visit our lab website; https://sites.google.com/site/brockdorfflab/