Molecular mechanisms of dosage compensation in Drosophila

• Applicant: Professor Dr. Peter Burkhard Becker
• Subject Area: Cell Biology
• Term: from 2001 to 2004
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5301542

Dosage compensation is a regulatory process of species with heteromorphic sex chromosomes that assures that X chromosomal genes are expressed to an equivalent extent from the single male X chromosome and two female X-chromosomes. Failure to increase the expression of genes residing on the male X chromosome by two fold is lethal for male Drosophila. Dosis compensation is an epigenetic process involving the modification of male X chromosome structure involving the association of the dosage compensation complex (DCC) with chromatin. DCC is a chromatin remodeling machinery composed of several enzymes as well as non-coding RNA. Dosis compensation involves the acetylation of histone H4 by MOF, a DCC-associated histone acetyl transferase. The histone modification leads to an increased transcription of X-linked genes in a process that is poorly understood, but likely to involve a loosening of higher order chromatin folding. The phenomenon of dosis compensation poses a number of important questions centering around (1) the targeting of chromatin remodeling factors to a restricted chromosomal domain, (2) the role of non-coding RNA in epigenetic regulatory phenomena and (3) the mechanisms by which histone modifications affect the structure and function of chromatin at the higher order structural level. Our aim is to answer these questions by reconstituting DCC and dosis-compensated chromatin from recombinant components in vitro, and by establishing an in vivo system for the dissection of the molecular determinants of DCC structure and function.

• DFG Programme: Research Grants