Regulation of cell-type-, stimulus- and promoter-specific transcription
Dr Simona SACCANI
Laboratory of transcription specificity, Institute for Research on Cancer & Aging (IRCAN), Nice, France
lundi 27 février 2017 - 11h00
- Auditorium, IGBMC
Invité(e) par Génomique fonctionnelle et cancer, Irwin DAVIDSON
The precise regulation of gene expression underlies the ability of all living organisms to respond to stimuli and is essential for metazoan development and differentiation. We are interested in understanding the molecular steps which impart specificity to transcriptional activation, and we focus on two fundamental questions: (1) how do often widely-expressed transcription factors (TFs) confer specific patterns of promoter activation?, and (2) how do distal-regulatory elements control gene activities in cis?
Using inducible gene activation by NFkB family TFs as a model, we have described how a single TF can drive promoter activation through 2 independent modes, and thereby enable distinct promoter context to impart precision to transcriptional output. Recent unpublished work has led to the discovery of a promoter ‘transducer’ factor which mediates this activity for many diverse TFs, and uncovered an unanticipated level of binding specificity arising from assembly of individual TF subunits into dimers, and we are exploring how this contributes to different aspects of gene regulation.
We have also addressed how modifications to chromatin can influence the function and accessibility of cis-regulatory elements, and shown how different methylation states of histone 3 lysine 9 (H3K9) can differentially regulate promoter and enhancer activities, and how these can be actively erased by specific demethylases in a stimulus-driven fashion. Current work in the laboratory is aimed at elucidating the genomic features which control chromatin modifications at cis-regulatory elements, and the mechanistic basis for their activities.