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Marie Curie Research Training Network
TAF-Chromatin |
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PROJECT OVERVIEW |
Regulation of gene expression at the transcriptional level is a key biological process in determining cell-type and signal specific gene expression patterns. The above objectives are mainly focused on proteins forming the regulatory networks that control fundamental biological processes in several different contexts. Successful execution of our goals, which combine interdisciplinary efforts, promises new breakthroughs in the field of transcription regulation, since they address novel aspects in the process, including:
| i. |
the specific functions of individual basal RNA polymerase II transcription complexes and how they participate in regulation of gene expression in vitro and in vivo, | |
| ii. | how do signal inducible transcription factors regulate the chromatin structure to allow transcription from specific target genes, | |
| iii. | how gene specific transcription is achieved during cell differentiation. | |
| iv. | how is the transcription process spatially organized in the eukaryotic nucleus? |
The proteins involved in the regulation of transcription can be grouped in four classes:
- Gene-specific transcription activators or repressors with sequence specific DNA binding properties. These proteins select genes for activation or repression.
- General (or basal) transcription factors that assemble at the core promoter regions. Their role is to show the RNA polymerase II where to start the mRNA synthesis
- Co-activators (or mediators) and co-repressors which via protein-protein interactions provide a molecular bridge between the above mentioned two types of proteins.
- Chromatin remodelling machines which change the DNA accessibility of the protein complexes mentioned above.
Because of the combinatorial nature of the transcriptional regulatory process, a virtually unlimited number of unique enhancer complexes can be assembled from a relatively small set of transcriptional activator proteins. The primary function of the activation domains exposed by the enhancer complexes is to interact with many components of the basal transcriptional apparatus. The weak linkage of the regulatory components and the high degree of flexibility inherent to the system promote the evolvability of unique control circuits. Our current view postulates that a virtually infinite number of transcriptional complexes can recruit the basal transcription machinery in a gene-specific manner to regulate precisely the expression of genes during differentiation, growth and development..
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