CHROMATINMOLEVOL · Molecular and evolutionary characterization of core and linker histone variants: mechanisms involved in altered chromatin conformations arising from pathological states
6РП — Действия „Мария Кюри“
- Период
- 2005-12-01 → 2008-11-30
- Финансиране от ЕС
- 186 670 €
- Участници
- 2
- Схема
- OIF
Линиите свързват координатора с партньорите.
Накратко на български
Хистоновите протеини и техните варианти (като H2A.X) се анализират при различни организми, за да се разбере как променят структурата на хроматина. Това помага да се разберат механизмите, които водят до патологични състояния в клетките.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
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.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
In eukaryotes the avaliability of the genetic information stored in the DNA is modulated by the interactions of this molecule with a broad spectrum of nuclear proteins such as histones and non-histone proteins. Histones are the main protein components of t he chromatin, where core histones organize DNA into nucleosome core particles and the linker histones bind to the regions contacting adjacent nucleosomes in the chromatin fiber. Although there has recently been a renewed interest in the functional and stru ctural characterization of histone variants, their role in the modulation of chromatin folding and dynamics is poorly understood. Histones H2A and H1 are characteristic for presenting the widest variability of variants among histones, including roles relat ed to DNA double-strand breaks repair, cell cycle checkpoints, and tumor supression. The present project represents a very innovative, high quality and multidisciplinary scientific work whose aim is to develop a molecular and evolutionary analysis of diffe rent core and linker histone proteins. The objetives proposed are: 1) the isolation and characterization of core and linker histone variants in vertebrate and protozoan lineages, 2) the molecular evolutionary analysis of core and linker histone variants to wards their functional diversification related to different chromatin structures, 3) the structural and functional characterization of chromatin complexes reconstituted from core histone variants including H2A.X and H2A.Z and further characterization of th e interactions of linker histones with chromatin. The analysis of such protein structures and the functional consequences of their modes of interaction with DNA will allow us to establish links with mechanisms involved in the altered chromatin conformation s arising from pathological states as cancer.
Оригинален текст от CORDIS (на английски).
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Данни: CORDIS, © Европейски съюз