Summary
Transcription factors (TFs) distinctly mark regions of the genome for expression and are the pillars of cell identity. Yet, even at the basic level of DNA recognition by TFs, we know very little about how this is achieved. In eukaryotes, all DNA-templated processes occur in chromatin; however, most studies elucidating the molecular mechanisms of transcription have been performed on histone-free DNA. In the proposed project, we will use TFs as centerpieces to understand how, in the circadian system, the interplay between transcriptional regulatory complexes and chromatin shapes the eukaryotic genome to control gene expression. Specifically, we will use biochemical approaches paired with functional genomics and cryo-EM (single particle and tomography) to investigate how histone identity affects TF-DNA engagement and how TFs and histone modifications influence chromatin organization across biological scales, from nucleotide sequence to chromatin structure in situ. We will exploit circadian time in mammalian cells and the unicellular green algae, Chlamydomonas to elucidate the dynamic gene regulation of a biological system under natural conditions. Using diverse model organisms will enable us to reveal common, conserved properties and processes. Ultimately, these studies will provide unique insight into the fundamental mechanisms of gene regulation while dissecting the molecular mechanisms of biological timekeeping.
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| Web resources: | https://cordis.europa.eu/project/id/101162145 |
| Start date: | 01-01-2025 |
| End date: | 31-12-2029 |
| Total budget - Public funding: | 1 624 563,00 Euro - 1 624 563,00 Euro |
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Original description
Transcription factors (TFs) distinctly mark regions of the genome for expression and are the pillars of cell identity. Yet, even at the basic level of DNA recognition by TFs, we know very little about how this is achieved. In eukaryotes, all DNA-templated processes occur in chromatin; however, most studies elucidating the molecular mechanisms of transcription have been performed on histone-free DNA. In the proposed project, we will use TFs as centerpieces to understand how, in the circadian system, the interplay between transcriptional regulatory complexes and chromatin shapes the eukaryotic genome to control gene expression. Specifically, we will use biochemical approaches paired with functional genomics and cryo-EM (single particle and tomography) to investigate how histone identity affects TF-DNA engagement and how TFs and histone modifications influence chromatin organization across biological scales, from nucleotide sequence to chromatin structure in situ. We will exploit circadian time in mammalian cells and the unicellular green algae, Chlamydomonas to elucidate the dynamic gene regulation of a biological system under natural conditions. Using diverse model organisms will enable us to reveal common, conserved properties and processes. Ultimately, these studies will provide unique insight into the fundamental mechanisms of gene regulation while dissecting the molecular mechanisms of biological timekeeping.Status
SIGNEDCall topic
ERC-2024-STGUpdate Date
24-11-2024
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