Final Activity Report Summary - CHROMATINMOLEVOL (Molecular and evolutionary characterisation of core and linker histone variants: mechanisms involved in (...) arising from pathological states) The project entitled 'Molecular and evolutionary characterisation of core and linker histone variants: mechanisms involved in altered chromatin conformations arising from pathological states' (CHROMATINMOLEVOL) was developed between December 2005 and November 2008 within the Sixth Framework Programme of the European Union in the Marie Curie Actions, Outgoing International Fellowships (MCA-OIF-021900), as a joint proposal between the University of A Coruna in Spain and the University of Victoria in Canada with Dr Jose M. Eirin-Lopez being the researcher (fellow). The central aim of the project focused towards the study of the variability of histone proteins and their corresponding genes across different organisms, leading to the subsequent study of the specialisation imparted by histones and histone variants to the chromatin structure. Three objectives were proposed for the project development: 1. isolation and characterisation of core and linker histone variants in vertebrate and protozoan lineages; 2. molecular analysis of the evolutionary aspects of core and linker histone variants responsible for their functional diversification and association with different chromatin structures; 3. structural and functional characterisation of chromatin complexes reconstituted from core histone variants including H2A.X H2A.Bbd and H2A.Z and further characterisation of the interactions of linker histones with chromatin in somatic and germinal cells. The most relevant results of the project included the characterisation of different histone proteins from molecular, biochemical and evolutionary perspectives, allowing for the study of their role in chromatin dynamics and metabolism. The long term evolutionary mechanisms guiding the evolution of histone family members along with other interacting proteins were studied and defined in the present work, as well as the functional constraints governing these changes. Furthermore, evolutionary links were discovered between linker histones and sperm chromosomal proteins (SNBPs). In addition, the concrete role of key core and linker histone variants in chromatin dynamics were further characterised, providing further insight into the processes involved in altered chromatin states arising from pathological states. Overall, the project derived results represented a very relevant contribution to the state of the art in the field of chromatin biology, posing new questions for the extension of the present work in future projects such as the 'ERC Ideas for Young Researchers', which was a proposal already presented by the candidate.
