Question

The differentiation of muscle cells from the somites (segments of mesoderm) of a developing embryo is controlled by myogenin, an helix-loop-helix gene regulatory protein that functions as a heterodimer with another member of the MyoD family of HLH proteins (see Figure A below). The activity of myogenin must be carefully controlled to prevent it from triggering premature expression of the muscle program of cell differentiation. The myogenin gene is turned on in advance of the time when it is needed, but myogenin is prevented from functioning by phosphorylation of its DNA-binding domain and by tight binding to

Id, an HLH protein that lacks a DNA-binding domain (see Figure B below). Explain how dimerization with Id and phosphorylation of the DNA-binding domain might act to keep myogenin nonfunctional. (2 pts)

Answer 1

DNA is a negatively charged molecule. DNA binding domains are positively charged. Phosphorylation of DNA binding domains adds a negative charge and creats steric problems. Addition of negative charge would add more repulsive force between the DNA and the protein interfering with it's function. A heterodimer formed between myogenin and truncated HLH protein lacking DNA binding domain would be unable to bind tightly with DNA because it would make only half of the necessary contacts.