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RSF governs silent chromatin formation via histone H2Av replacement
Authors:Hanai Kazuma  Furuhashi Hirofumi  Yamamoto Takashi  Akasaka Koji  Hirose Susumu
Affiliation:1Department of Developmental Genetics, National Institute of Genetics, Shizuoka-ken, Japan;2Department of Mathematical and Life Science, Graduate School of Science, Hiroshima University, Higashi-Hiroshima, Japan;3Misaki Marine Biological Station, Graduate School of Science, The University of Tokyo, Miura, Kanagawa, Japan;European Molecular Biology Laboratory, Germany
Abstract:Human remodeling and spacing factor (RSF) consists of a heterodimer of Rsf-1 and hSNF2H, a counterpart of Drosophila ISWI. RSF possesses not only chromatin remodeling activity but also chromatin assembly activity in vitro. While no other single factor can execute the same activities as RSF, the biological significance of RSF remained unknown. To investigate the in vivo function of RSF, we generated a mutant allele of Drosophila Rsf-1 (dRsf-1). The dRsf-1 mutant behaved as a dominant suppressor of position effect variegation. In dRsf-1 mutant, the levels of histone H3K9 dimethylation and histone H2A variant H2Av were significantly reduced in an euchromatic region juxtaposed with heterochromatin. Furthermore, using both genetic and biochemical approaches, we demonstrate that dRsf-1 interacts with H2Av and the H2Av-exchanging machinery Tip60 complex. These results suggest that RSF contributes to histone H2Av replacement in the pathway of silent chromatin formation.
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