On the molecular interplay of a pair of human Transcription Factors
Dr Andrea BERNARDINI
Dipartimento di Bioscienze Università degli Studi di Milano, Italy
Friday, September 18th 2020 - 11 a.m.
- Meeting room 4004, IGBMC
Hosted by L. Tora team
Complex cells need complex mechanisms to fine tune the activity of their genes in response to different molecular environments and internal sensors. Among the many layers of control, recognition of DNA-encoded regulatory elements by a diversified class of proteins – named Transcription Factors (TFs) – represents the initial step for nucleating a productive transcriptional event. The specificity of this process is increased by its combinatorial nature, whereby the activity of each gene is modulated by the specific combination of TFs that bind the correspondent regulatory regions.
TFs have evolved strategies to cooperate with neighboring TFs and convey signals to the basal transcriptional apparatus. Yet, the molecular mechanisms that underlie these processes are far from being well understood.
I will present observations gathered in our lab on the molecular interplay between a pair of human TFs: the histone-like ‘pioneer’ NF-Y and USF1, a member of the bHLH family. Genomic observations highlighted a striking – stereo-specific – co-localization of their binding sites in regulatory regions. We provided evidence for NF-Y-dependent USF1 chromatin occupancy in vivo, strong DNA-binding cooperativity in vitro and transcriptional synergy on natural target promoters. We further dissected the domains mediating their interplay on DNA through structural and biochemical approaches, revealing the contribution of an intrinsically disordered region to this interplay.
Moreover, I will present an outline to other ongoing projects related to NF-Y dynamics in living cells, evolutionary history of its splicing isoforms and biophysical approaches to study TFs-DNA interactions.