Selected publications

• Law Martin J, Lower Karen M, Voon Hsiao PJ, Hughes Jim R, Garrick David, Viprakasit Vip, Mitson Matthew, De Gobbi Marco, Marra Marco, Morris Andrew, Abbott Aaron, Wilder Steven P, Taylor Stephen, Santos Guilherme M, Cross Joe, Ayyub Helena, Jones Steven, Ragoussis Jiannis, Rhodes Daniela, Dunham Ian, Higgs Douglas R, and Gibbons Richard J (2010) ATR-X syndrome protein targets tandem repeats and influences allele-specific expression in a size-dependent manner. Cell, 143(3):367-78.

• Goldberg Aaron D, Banaszynski Laura A, Noh Kyung-Min, Lewis Peter W, Elsaesser Simon J, Stadler Sonja, Dewell Scott, Law Martin, Guo Xingyi, Li Xuan, Wen Duancheng, Chapgier Ariane, DeKelver Russell C, Miller Jeffrey C, Lee Ya-Li, Boydston Elizabeth A, Holmes Michael C, Gregory Philip D, Greally John M, Rafii Shahin, Yang Chingwen, Scambler Peter J, Garrick David, Gibbons Richard J, Higgs Douglas R, Cristea Ileana M, Urnov Fyodor D, Zheng Deyou, and Allis C D (2010) Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell, 140(5):678-91.

• Gibbons R J, McDowell T L, Raman S, O'Rourke D M, Garrick D, Ayyub H, and Higgs D R (2000) Mutations in ATRX, encoding a SWI/SNF-like protein, cause diverse changes in the pattern of DNA methylation. Nat Genet, 24(4):368-71.

• Gibbons Richard J, Pellagatti Andrea, Garrick David, Wood William G, Malik Nicola, Ayyub Helena, Langford Cordelia, Boultwood Jacqueline, Wainscoat James S, and Higgs Douglas R (2003) Identification of acquired somatic mutations in the gene encoding chromatin-remodeling factor ATRX in the alpha-thalassemia myelodysplasia syndrome (ATMDS). Nat Genet, 34(4):446-9.

• Xue Yutong, Gibbons Richard, Yan Zhijiang, Yang Dafeng, McDowell Tarra L, Sechi Salvatore, Qin Jun, Zhou Sharleen, Higgs Doug, and Wang Weidong (2003) The ATRX syndrome protein forms a chromatin-remodeling complex with Daxx and localizes in promyelocytic leukemia nuclear bodies. Proc Natl Acad Sci U S A, 100(19):10635-40.

Dr Richard Gibbons

In eukaryotes, genes are packed into chromatin.  It is becoming clear that, rather than just being a DNA-packaging vehicle, chromatin is a dynamic and active participant in regulating transcription of the eukaryotic genome.

Our group has an interest in the function of a particular protein, ATRX, that appears to play a role in regulating gene expression through its interaction with chromatin. It belongs to the SNF2 family of DNA-dependent ATPases and putative helicases. Members of this family appear to be involved in a wide range of cellular functions but a common thread is their ability to remodel chromatin.

Mutations in the ATRX gene give rise to a form of syndromal mental retardation known as X-linked alpha thalassaemia mental retardation (ATR-X) syndrome.

HbH inclusions in alpha thalassaemia

It is characterised by severe learning difficulties, a characteristic facial appearance, abnormalities of genital development and alpha thalassaemia.  Somatic mutations in ATRX are found in an acquired form of alpha thalassaemia associated with myelodysplasia.  In these two conditions, the alpha thalassaemia, which is a form of anaemia resulting from defective production of alpha globin, is due to down-regulation of alpha globin gene expression and this points to a role of ATRX in regulating transcription.

Child with ATR-X syndrome

The overall aim of this programme is to determine the role of such proteins in the regulation of gene expression and their involvement in human disease.