Ray-Gallet D, Woolfe A, Vassias I, Pellentz C, Lacoste N, Puri A, Schultz DC, Pchelintsev NA, Adams PD, Jansen LE, Almouzni G. (2011) Dynamics of histone H3 deposition in vivo reveal a nucleosome gap-filling mechanism for H3.3 to maintain chromatin integrity. Molecular Cell.44:928-941   [LINK]
Woolfe A, Mullikin JC and Elnitski L. (2010) Genomic features defining exonic variants that modulate splicing. Genome Biology.11:R20   [PDF]
McEwen G, Goode DK,Parker HJ,Woolfe A,Callaway H and Elgar G. (2009) Early evolution of conserved regulatory sequences associated with development in vertebrates. PLoS Genetics.5:e1000762   [PDF]
Woolfe A, Goode D, Cooke J, Callaway H, Smith S, Snell P, McEwen G and Elgar G. (2007) CONDOR: a database resource of developmentally-associated conserved non-coding elements. BMC Developmental Biology.7:100   [PDF]
Woolfe A and Elgar G. (2007) Comparative genomics using Fugu reveals insights in regulatory subfunctionalization. Genome Biol.8:R53   [PDF]
McEwen GK, Woolfe A, Goode G, Vavouri T, Callaway H and Elgar G. (2006) Ancient duplicated conserved noncoding elements in vertebrates: a genomic and functional analysis. Genome Res.16: 5-10   [PDF]
Vavouri T, McEwen GK, Woolfe A, Gilks WR and Elgar G. (2006) Defining a genomic radius for long-range enhancer action: duplicated conserved non-coding elements hold the key. Trends Genet.22: 5-10  [Link]
Woolfe A, Goodson M, Goode DK, Snell P, McEwen GK, Vavouri T, Smith SF, North P, Callaway H, Kelly K, Walter K, Abnizova I, Gilks W, Edwards YJ, Cooke JE, Elgar G. (2005). Highly Conserved Non-Coding Sequences Are Associated with Vertebrate Development. PLoS Biol. 2005 Jan; 3(1): e7   [PDF]
Study of the regulatory architecture of vertebrate genomes is providing one of the biggest challenges of the post-genomic era. Fish-mammal genomic comparisons have proved powerful in identifying conserved non-coding elements likely to be distal cis-regulatory modules such as enhancers, silencers or insulators. In addition, there is increasing evidence that such elements are strongly associated with genes involved in transcriptional regulation and development. Here, by using a targeted multiple-alignment strategy of orthologous genomic sequence from the Japanese pufferfish Fugu rubripes together with that of a number of mammals, I identified a large set of conserved non-coding elements (CNEs) surrounding more than 100 regulator genes involved in early development. To facilitate a further in-depth analysis of these elements for this study and public use, a relational database CONDOR (database of COnserved NoncoDing Orthologous Regions) and front-end were designed to store and access this data together with associated functional data issuing from wet-lab experimentation. The database can be accessed at condor.nimr.mrc.ac.uk.
Using the database, I studied a number of evolutionary and sequence-based aspects of these intriguing elements and found they are distinct in many ways from other functional sequences such as coding exons. In addition, a small proportion of these elements show sequence similarity to other parts of the genome and appear to be associated with nearby paralogous genes that date back to the large-scale duplication events at the origin of vertebrates. Finally I carried out a comparative analysis of CNEs identified around seven pairs of Fugu developmental genes that derive from whole-genome duplication early in the teleost lineage. Presence of shared and distinct CNEs between duplicated genes suggest they are likely to have undergone a process of regulatory subfunctionalisation the extent of which differs between duplicate pairs.