Chromatin Organisation and the Regulation of Gene Expression
The basis of embryonic development lies in the spatiotemporal control of gene expression. Cis-regulatory elements, also known as enhancers, regulate the embryonic location and the developmental stage of gene expression. This precision in gene expression is controlled by higher order and local chromatin organisation, and the sequence composition of the enhancer. A catalogue of cis-regulatory variations associated with species evolution, individual variation and predisposition to disease has emerged over the last several years. Our aims are to understand the regulatory mechanisms responsible for gene activation and the regulatory processes affected by mutations that cause congenital abnormalities.
We focus our studies on the genomic topological domain containing the cis-regulatory elements for the sonic hedgehog (Shh) gene. Shh is a signalling molecule that influences the development of many embryonic tissues from facial and brain morphogenesis to limb formation. The enhancer elements that drive expression in these diverse tissues are scattered across >1Mb of DNA and lie in a gene desert and inside two other unrelated genes. Within this domain is a limb specific enhancer, and brain enhancers and regulatory mutations involving these enhancers cause human abnormalities. Our studies focus on the dynamics of promoter recognition by long-distance cis-regulators, higher order chromatin conformation that underpins the regulatory domain, the role of local chromatin on enhancer activation and the information encoded in the enhancer that drives gene activation.
|Professor Robert Hill||Group Leader|
|Dr Laura Lettice||Senior Scientist|
|Dr Silvia Peluso||Postdoctoral Fellow|
|Adam Douglas||Postgraduate Student|
|Zoe Crane-Smith||Postgraduate Student|
|Dr Alison Hill||Research Assistant|
|Carlo DeAngelis||Research Assistant|
|Paul Devenney||Research Assistant|
Mammalian development, congenital abnormalities, long-range gene regulation, chromatin structure
genetics, molecular biology and developmental biology