Regulation of ISWI-type chromatin remodeling complexes by phosphorylation.

Snf2H/L are the catalytic subunits of complexes that belong to the ISWIfamily of chromatin remodeling complexes, which are essential players in DNA replication and transcription. NIPP1 has a major function in the regulation of cell proliferation and differentiation but its exact mechanism of action is not known. My recent data revealed that the ForkHead Associated (FHA) domain of NIPP1 interacts directly with Snf2H. The first goal of this PhD project is to further map the determinants and regulation of the NIPP1-Snf2H interaction. As it is known that NIPP1 interacts directly with Snf2H, it needs to be clarified which motif(s) of Snf2H areresponsible for the interaction en whether this interaction is regulated by phosphorylation. Furthermore, the interaction between NIPP1 and Snf2L will be investigated. My second goal is to identify the Snf2H/L complexes that bind NIPP1. The third goal is to characterize the function of the NIPP1-Snf2H/L interaction. Therefore, I will examine whether (1) NIPP1 has an effect on the catalytic activity of Snf2H/L, (2) the chromatintargeting of Snf2H/L is regulated by NIPP1 and (3) NIPP1 interferes with established functions of Snf2H/L. In short, I want to structurally andfunctionally characterize the NIPP1-Snf2H/L interaction. This characterization will contribute to the elucidation of the functions of NIPP1 andits FHA ligands.

Keywords:FHA ligands, NIPP1, Reversible protein phosphorylation, ISWI complexes, Chromatin remodeling

Disciplines:Systems biology

Project type:PhD project