CHROMA · Complex chromatin systems in the test tube
6РП — Действия „Мария Кюри“
- Период
- 2007-02-01 → 2009-01-31
- Финансиране от ЕС
- 80 000 €
- Участници
- 1
- Схема
- EIF
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Накратко на български
Хистоните са протеини, които организират ДНК, а модификациите им определят достъпа до генетичната информация. Разбирането на тези механизми помага да се разбере епигенетиката – как се променя работата на гените, без да се променя самата ДНК последователност.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - CHROMA (Complex chromatin systems in the test tube)
In all cells of our bodies DNA complex basic proteins can be found, the so-called histones. These highly conserved proteins not only organise and protect the genetic information, but are also crucially involved in all biological processes involving DNA. In this aspect, a large number of different post-translational histone modifications direct the availability and accessibility of the DNA. While many histone modifications could be linked to different biological phenomena and signal transduction pathways, the molecular working mechanisms of most histone modifications are still not understood. In the CHROMA research project recombinant test tube systems for the analysis of chromatin regulatory pathways could be established. Based on defined components the researchers have set up small elements of chromatin containing chemically defined histone modifications. Using sophisticated biochemical and biophysical assay systems the functional properties of the artificial chromatin elements could be defined. In particular, the researchers could characterize the working mechanism of several different proteins that interact and thereby read-out distinct histone modifications. Further, it could be shown that recruitment of different factors in dependence of distinct histone modifications to the artificial chromatin changes its overall conformation and structure. It is proposed that such changes have profound effects onto the functional properties of the underlying DNA elements thereby controlling the functionality of the genome. Overall, the studies have likely far-reaching implications for our understanding of epigenetic regulatory mechanisms that is pathways that result in inheritable changes in gene expression profiles without changes of the DNA sequence or content. It is thought that many diseases and especially cancer have epigenetic components.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Chromatin is the physiological template of genetic information controlling the capacity of a cell's genome to store, release, and inherit biological information. The basic unit of chromatin is the nucleosome: a stretch of DNA wrapped around a core of histone proteins. Post-translational modifications of histones have emerged as key in regulating chromatin structure and dynamics and are thought to crucially control genome activity. Whereas correlative studies have begun to establish links between several states of chromatin, various histone modifications, and diverse biological processes, our knowledge of how certain histone modifications exert their biological effects on a molecular level is extremely limited.One of the principles emerging from our previous studies is that certain histone marks are acting via the recruitment of sequence and modification specific binding proteins (effectors). To get a detailed understanding of the signalling principles within the histone modification/effector protein-signalling network, we propose the reconstitution of complex chromatin systems in vitro. In particular, we intend to analyse the readout and the chromatin effects of three intriguing histone methyl-lysine marks (H3 Lys 9, H3 Lys 27, and H4 Lys 20) that have distinct cellular functions and might work via recruitment of HP1 (heterochromatin protein 1), Pc (Polycomb) and MBT (malignant brain tumour) proteins, respectively. We anticipate that our studies will result in a detailed understanding of fundamental epigenetic" regulatory pathways that cause inheritable changes in gene function and expression, but do not involve changes in DNA sequence.We believe that the implications of the proposed research could be far reaching as it is becoming clear that many human disease-states, and in particular cancer have an epigenetic component. This estimation is substantiated by the high promise of experimental drugs targeting histone-modifying enzymes in the treatment of human tumours."
Оригинален текст от CORDIS (на английски).
Участници
- MAX-PLANCK-GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V. · MUENCHENКоординаторГермания
Връзки
Данни: CORDIS, © Европейски съюз