The USR domain of USF1 mediates NF-Y interactions and cooperative DNA binding.

The trimeric CCAAT-binding NF-Y is a "pioneer" Transcription Factor -TF- known to cooperate with neighboring TFs to regulate gene expression. Genome-wide analyses detected a precise stereo-alignment -10/12 bp- of CCAAT with E-box elements and corresponding colocalization of NF-Y with basic-Helix-Loop-Helix (bHLH) TFs. We dissected here NF-Y interactions with USF1 and MAX. USF1, but not MAX, cooperates in DNA binding with NF-Y. NF-Y and USF1 synergize to activate target promoters. Reconstruction of complexes by structural means shows independent DNA binding of MAX, whereas USF1 has extended contacts with NF-Y, involving the USR, a USF-specific amino acid sequence stretch required for trans-activation. The USR is an intrinsically disordered domain and adopts different conformations based on E-box-CCAAT distances. Deletion of the USR abolishes cooperative DNA binding with NF-Y. Our data indicate that the functionality of certain unstructured domains involves adapting to small variation in stereo-alignments of the multimeric TFs sites.

Clustering of Lifestyle Risk Factors among Algerian Adolescents: Comparison between Urban and Rural Areas: GSHS Data.

OBJECTIVE: Compare the clustering of LBRs between urban and rural Algerian adolescents. DESIGN: Data of this cross-sectional study was derived from the Global School-based Health Survey (GSHS). A self-administered, anonymous questionnaire was filled out by 4532 adolescents (11-16 years), which addressed LBRs of NCDs. Life style behavioral risk factors (LBRs) clustering was measured by the ratios of observed (O) and expected (E) prevalence of one or more simultaneously occurring LBRs for urban and rural areas separately. Multivariate logistic regression was performed to examine the association of LBRs as dependent variable with demographic variables (location, age, gender). RESULTS: The most common LBR was physical inactivity (84.6%: 50.9% for urban and 49.1% for rural). Adolescents in urban areas had a higher prevalence of two (56.8% vs. 43.2%) and three and more (61.3% vs. 38.7%) LBRs than in rural areas. In urban areas, a significant positive association was found between (low fruit and vegetable consumption + physical inactivity) [2.06 (1.61-2.64)] and (high SB + smoking) [2.10 (1.54-2.76)], while (physical inactivity + high SB) [0.70 (0.54-0.91)] showed a significant negative association. In rural areas, (high SB + overweight/obesity) [1.49 (1.09-2.04)] had a significant positive association. While, (low fruit and vegetable consumption + high SB) [0.75 (0.60-0.94)], (physical inactivity + high SB) [0.65 (0.49-0.86)], and (physical inactivity + smoking) [0.70 (0.49-0.99)] had a negative association. CONCLUSIONS: Several socio-demographic factors have been identified to play a role in LBRs clustering among Algerian adolescents. Results of the study suggest the development of intervention aiming to tackle different LBRs rather than focusing on a single LBR.

High Conformational Flexibility of the E2F1/DP1/DNA Complex.

The E2F1 transcription factor is a master regulator of cell-cycle progression whose uncontrolled activation contributes to tumor cells growth. E2F1 binds DNA as a heterodimer with DP partners, resulting in a multi-domain quaternary-structure complex composed of DNA binding domains, a coiled coil domain and a marked box domain separated by short linkers. Building on the 3D knowledge of the single domains of E2F and DPs, we characterized the structure and dynamics of the complete E2F1/DP1/DNA complex by a combination of small-angle X-ray scattering and molecular dynamics simulations. It shows an asymmetric contribution of the dynamics of the two proteins. Namely, the coiled-coil domain leans toward the DP1 side of the complex; the DP1 loop between α2 and α3 of the DBD partially populates a helical structure leaning far from the DNA and in the same direction of the coiled-coil domain; and the N-terminal disordered region of DP1, rich in basic residues, contributes to DNA binding stabilization. Intriguingly, tumor mutations in the flexible regions of the complex suggest that perturbation of protein dynamics could affect protein function in a context-dependent way. Our data suggest fundamental contributions of DP proteins in distinct aspects of E2F biology.