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Julie Ahringer

ahringerJulie Ahringer PhD FMedSci, Wellcome Trust Senior Research Fellow, Professor of Genetics and Genomics, Member of the Department of Genetics

Ahringer Group website | Europe PMC | Pubmed

 

 

 

The regulation of chromatin structure and function

2016 AhringerHow 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. 

Selected publications:

• 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.

 groupAhringer2015

Plain English

The DNA of our genome is found in the nucleus and is bound by many different proteins in a conglomeration termed chromatin. Within chromatin, these proteins regulate everything that happens to the genome, for example they repair it when it is damaged, and they turn the appropriate genes on or off.

We now know that human diseases can be caused by defects in chromatin, including developmental defects, ageing, and cancer, and drugs that target chromatin proteins have shown promise in cancer treatment. However the functions of few chromatin proteins are understood. Deepening our basic knowledge of chromatin is critical for understanding normal development and has potential highlight new therapeutic avenues.

We are studying chromatin function in the model organism C. elegans, a small nematode that has many advantageous experimental features. Importantly, the chromatin proteins of C. elegans are very similar to those of humans. We study the structure and function of C. elegans chromatin and investigate the functions of C. elegans counterparts of chromatin proteins implicated in human disease. Our work will improve our basic knowledge of how the genome works and further our understanding of chromatin proteins important for human health.

Co-workers

Alex Appert • Fanélie Bauer • Chiara Cerrato • Yan Dong • Tessa Gaarenstroom • Csenge Gal • Ni Huang • Jürgen Jänes • Florence Leroy • Alicia McMurchy • Wei Qiang Seow • Garima Sharma • Przemyslaw Stempor