Shinya Sakaguchi, PhD
PostDoc (since 05/2009)
phone: +43-1-40160-65005
fax: +-43-1-40160-965006
email: shinya.sakaguchi@meduniwien.ac.at
Molecular analysis of the zinc finger factor MAZR
Cell fate specifications during thymocyte differentiation are linked with the tightly controlled expression of CD4 and CD8 coreceptor molecules. The expression of the adjacent genes Cd8a and Cd8b is controlled by at least five developmental stage-, subset- and lineage-specific cis- regulatory elements. Our laboratory recently identified with yeast one-hybrid screens the BTB/POZ-domain containing zinc finger protein MAZR (Myc-associated Zn finger related factor) as an E8 II core enhancer binding protein. MAZR ( encoded by the Zfp278 gene) is highly expressed in DN thymocytes and its expression is down-modulated with progressive thymocyte differentiation. We could show that Cd8 enhancers recruit MAZR to the Cd8ab gene complex and that MAZR interacts with corepressor N-CoR (nuclear receptor corepressor) complexes in DN thymocytes. Enforced expression of MAZR during T cell development unexpectedly resulted in variegated expression of CD8 in DP thymocytes, suggesting that MAZR negatively regulates chromatin modifications at the Cd8 gene loci required for the activation of CD8 expression. In my PhD project, I am performing gain and loss of function approaches to further analyze the role of MAZR.