Searle Scholar Profile : Mitzi I. Kuroda (1992)

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	Mitzi I. Kuroda Professor Department of Genetics Harvard University Center for Genetics and Genomics New Research Building, Room 168 77 Avenue Louis Pasteur Boston, MA 02115 Phone: 617-525-4520 Fax: 617- 525-4522 E-mail: mkuroda@genetics.med.harvard.edu Personal Homepage 1992 Searle Scholar

Coordinate gene regulation is of fundamental importance to development in all organisms. A striking example is dosage compensation, in which X linked gene expression is equalized in males (XY) and females (XX). In Drosophila, dosage compensation increases transcription of X-linked genes in males, is essential for male viability, and is correlated with a specialized chromatin composition of the male X chromosome. To define the biochemical mechanism responsible for dosage compensation we study the trans-acting factors required in males to increase X-linked transcription. We have focused on MSL proteins encoded by the maleless and male-specific lethal-1, -2, and -3 genes. When polytene chromosomes are spread to analyze the proteins bound to them, the MSL proteins are associated specifically with the male X chromosome. In addition, a specific isoform of histone H4, acetylated at Lys-16 (H4Ac16) is also localized almost exclusively to the male X chromosome. Since histone acetylation is correlated with gene expression in several systems, these data suggest that altered chromatin structure is involved in dosage compensation. Consistent with this hypothesis, we have found that the presence of H4Ac16 on the male X chromosome is dependent on the wild type MSL functions. We are currently pursuing genetic and biochemical studies to determine how these regulators function to increase transcription of the male X chromosome. Our findings should be relevant to understanding regulation of functional states of chromatin during development.