Julie Ahringer PhD FMedSci, Wellcome Trust Senior Research Fellow, Professor of Genetics and Genomics, Member of the Department of Genetics
The regulation of chromatin structure and function
How is chromatin regulated during development for correct cell fates and specific transcription? All nuclear events take place in the context of chromatin, the organisation of genomic DNA with histones and hundreds of associated proteins and RNAs. Regulation of the composition and structure of chromatin controls transcription and all other nuclear processes, and is important for cell fate decisions, the expression of cell identity, the maintenance of pluripotency, and the transformation to cancer.
We use C. elegans to study chromatin regulation in gene expression and genome organisation in a whole- organismal context. This model has many advantages: a complement of core chromatin factors very similar to that of humans, a well- annotated genome 30 times smaller than the human genome, efficient high-throughput RNA interference for loss-of-function studies, and well-characterised cell fates.
We apply genetics, high-throughput genomics and computational approaches to a range of problems in chromatin biology and transcriptional control, such as genome organisation, promoter and enhancer function, roles of histone modifications, heterochromatin formation and function, and the regulation of chromatin in developmental transitions.
• Latorre I et al. (2015) The DREAM complex promotes gene body H2A.Z for target repression. Genes Dev 29: 495–500.
• Ho JW, modENCODE consortium, et al. (2014) Comparative analysis of metazoan chromatin architecture. Nature 512: 449–452.
• Chen, A-J et al. (2014) Extreme HOT regions are CpG dense promoters in C. elegans and human. Genome Research 24: 1138–1146.
• Chen RA-J, Down TA, Stempor P, Chen QB, Egelhofer TA, Hillier LW, Jeffers TE and Ahringer J (2013) The landscape of RNA polymerase II transcription initiation in C. elegans reveals enhancer and promoter architectures, Genome Research 8, 1339-47
• Fievet BT*, Rodriguez J*, Naganathan S, Lee C, Zeiser E, Ishidate,T, Shirayama M, Grill S and Ahringer J (2012) Systematic genetic interaction screens uncover cell polarity regulators and functional redundancy. Nature Cell Biology 15 (1), 103-112
• Vielle A, Lang J, Dong Y, Ercan S, Kotwaliwale C, Rechtsteiner A, Appert A, Chen QB, Dose A, Egelhofer T, Stempor P, Dernburg A, Lieb J, Strome S and Ahringer J (2012) H4K20me1 contributes to downregulation of X-linked genes for C. elegans dosage compensation. PLoS Genetics (9): e1002933
• Gerstein MB, modENCODE Consortium, Ahringer J, Strome S, Gunsalus KC, Micklem G, Liu XS, Reinke V, Kim SK, Hillier LW, Henikoff S, Piano F, Snyder M, Stein L, Lieb JD, Waterston RH. (2010) Integrative Analysis of the Caenorhabditis elegans Genome by the modENCODE Project. Science 330, 1775-87.