Summary
Histones are the major structural proteins of eukaryotic DNA. Two copies each of the core histones, H2A, H2B, H3 and H4, form the core nucleosome, the basic unit of chromatin. Histone tails protrude from the nucleosome structure and are subject to a variety of post-translational modifications on multiple residues, including methylation, acetylation, phosphorylation, sumoylation, ubiquitination and polyribosylation. These histone modifications dictate local and global structure of chromatin, rendering it active and decondensed (‘euchromatic’) or suppressed and compact (‘heterochromatic’) by the recruitment of chromatin-binding proteins that recognize and associate with specific modifications. Histone modifications are therefore the basic regulatory unit of gene expression, genomic silencing, developmental programs, cell division and essentially all cellular processes. Understanding this so-called ‘epigenetic’ landscape is therefore vital for all biological mechanisms. Currently a Western blot is required in order to determine the state of each of the dozens of different histone modifications. Because of the growing number of histone modifications, this procedure is time consuming and labour intensive. Here I suggest to develop an antibody microarray to monitor the levels of all histone modifications simultaneously. This method will be essentially useful for any tissue or cell type in any biological process, for diagnosis, prognosis and drug screening. In addition to basic research, our platform will enable fast and reliable screening for epigenetic effects of existing and novel drugs. We believe that such a product could serve many drug companies interested in direct and indirect effects of epigenetic and non-epigentic drugs.
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| Web resources: | https://cordis.europa.eu/project/id/680600 |
| Start date: | 01-10-2015 |
| End date: | 31-03-2017 |
| Total budget - Public funding: | 150 000,00 Euro - 150 000,00 Euro |
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Original description
Histones are the major structural proteins of eukaryotic DNA. Two copies each of the core histones, H2A, H2B, H3 and H4, form the core nucleosome, the basic unit of chromatin. Histone tails protrude from the nucleosome structure and are subject to a variety of post-translational modifications on multiple residues, including methylation, acetylation, phosphorylation, sumoylation, ubiquitination and polyribosylation. These histone modifications dictate local and global structure of chromatin, rendering it active and decondensed (‘euchromatic’) or suppressed and compact (‘heterochromatic’) by the recruitment of chromatin-binding proteins that recognize and associate with specific modifications. Histone modifications are therefore the basic regulatory unit of gene expression, genomic silencing, developmental programs, cell division and essentially all cellular processes. Understanding this so-called ‘epigenetic’ landscape is therefore vital for all biological mechanisms. Currently a Western blot is required in order to determine the state of each of the dozens of different histone modifications. Because of the growing number of histone modifications, this procedure is time consuming and labour intensive. Here I suggest to develop an antibody microarray to monitor the levels of all histone modifications simultaneously. This method will be essentially useful for any tissue or cell type in any biological process, for diagnosis, prognosis and drug screening. In addition to basic research, our platform will enable fast and reliable screening for epigenetic effects of existing and novel drugs. We believe that such a product could serve many drug companies interested in direct and indirect effects of epigenetic and non-epigentic drugs.Status
CLOSEDCall topic
ERC-PoC-2015Update Date
27-04-2024
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