John Gurdon Group. Cell Reprogramming

Address

Keywords

Deoxyadenosine methylation, DNA modification, methylation, novel DNA modifications, adenosine

Models

We have discovered that deoxyadenosine can be methylated in various mammalian genomes, such as frogs, mouse and humans. We are using mass spectrometry and DNA immunoprecipitation to identify, quantify and describe the characteristics and function of this novel DNA modification in vertebrate genomes. Most of the vertebrate epigenetic modifications studies focus on histone and RNA, while modifications affecting directly DNA have mostly been ignored. With the tools we have independently developed, we will be able to study and further characterize direct DNA modifications and study their function.

Techniques

DNA immunoprecipitation, SMRT-Sequencing, RNA sequencing,

Collaborations outside COST

University of Cambridge, UK (Dr. C. Frezza) Sanger Institute, University of Cambridge, UK (Dr. M. Quail)

Short description of ongoing research projects

We are focussing on understanding furhter characteristics of methylated deoxyadenosines, as well as elucidating their function. All this has great potential: Since methylated deoxyadenosines alter DNA directly, it is likely that any misregulation might have strong effects on the genome, transcription and ultimately human health. For example, changes to deoxycytidine methylation, a direct DNA modification, were key for a better understanding of gene expression and various diseases such as cancer.

Publications

1. Koziol MJ, Bradshaw CR, Allen GE, Costa ASH, Frezza C, Gurdon JB. Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications. Nature Structural & Molecular Biology, 2015, doi: 10.1038/nsmb.3145
2. Koziol MJ, Gurdon JB. TCTP in development and cancer. Biochemistry Research International, 2012, doi: 10.1155/2012/105203
3. Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell, 2010, doi: 10.1016/j.cell.2010.06.040
4. Koziol MJ, Rinn JL. RNA traffic control of chromatin complexes. Current Opinions in Genetics & Development, 2010, doi: 10.1016/j.gde.2010.03.003
5. Koziol MJ, Garrett N, Gurdon JB. Tpt1 activates transcription of Oct4 and Nanog in transplanted somatic nuclei. Current Biology, 2007, doi: 10.1016/j.cub.2007.03.062

Other activities of potential interest to others

In addition to the experience described above, I have worked in the field of RNA, in particular non-long coding RNA, as well as nuclear reprogramming, pluripotency and early development.