MRC Human Genetics Unit
Medical Research Council Human Genetics Unit

Robert Hill Research Group

Chromatin Organisation and the Regulation of Gene Expression

B.hill
Professor Robert Hill

Section: Disease Mechanisms

Research in a Nutshell 

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.

 

Research Programme

 

B.Hill group

People

 

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

Contact

Bob.Hill@igmm.ed.ac.uk

Collaborations

  • Professor Wendy Bickmore, MRC Human Genetics Unit, University of Edinburgh
  • Professor Andrew Jackson, MRC Human Genetics Unit, University of Edinburgh
  • Dr Matthew Towers, University of Sheffield
  • Dr Mark Ditzel, Cancer Research UK Edinburgh Centre

Partners and Funders

  • Medical Research Council

 

Scientific Themes

Mammalian development, congenital abnormalities, long-range gene regulation, chromatin structure

Technology Expertise

genetics, molecular biology and developmental biology