1. Elucidation of the regulatory mechanisms underlying epigenetics: In multicellular organisms, expression patterns of genes should be maintained stably through and after cell division. These phenomena are termed “epigenetics”. Using Drosophila, we are trying to elucidate the regulatory mechanisms underlying epigenetics through molecular analyses of factors involved in Position Effect Variegation and regulation of Hox gene expression.
2. Biological significance of DNA supercoiling factor (SCF) and SPTT6: SCF is a protein capable of generating negative supercoils on DNA in conjunction with topoisomerase II. We found that SCF plays a key role in dosage compensation of male X chromosome in Drosophila. We are also analyzing biological role of SPT6 in multicellular organisms.
3. Mechanism of the coordinate cell movement during gastrulation: Gastrulation is a common step in animal development, where many cell groups move in a dynamic manner. We are studying on mechanism of the coordinate cell movement focusing on heterotrimeric G proteins in Drosophila.

GAGA factor and FACT-dependent replacement of K9-methylated histone H3 by H3.3 counteracts the
heterochromatin spreading.

Shimojima, T., Okada, M., Nakayama, T., Ueda, H., Okawa, K., Iwamatsu, A., Handa, H. and Hirose, S. (2003). Drosophila FACT contributes to Hox gene expression through physical and functional interactions with GAGA factor. Genes Dev. 17, 1605-1616.

Saunders, A., Werner, J., Andrulis, E. D., Nakayama, T., Hirose, S., Reinberg, D. and Lis, J. T. (2003). Tracking FACT and RNA polymerase II elongation complex through chromatin in vivo. Science 301, 1094-1096.

Jindra, M., Gaziova, I., Uhlirova, M., Okabe, M., Hiromi, Y. and Hirose, S. (2004). Coactivator MBF1 preserves the redox-dependent AP-1 activity during oxidative stress in Drosophila. EMBO J. 23, 3538-3547.

Furuhashi, H., Nakajima, M. and Hirose, S. (2006). DNA supercoiling factor contributes to dosage compensation in Drosophila. Development, 133, 4475-4483.　

>Petruck, S., Sedkov, Y., Riley, K. M., Hodgson, J., Schwisguth, F., Hirose, S., Jaynes, J. B., Brock, H. W. and Mazo, A. (2006). Transcription of bxd non-coding RNAs promoted by Trithorax represses Ubx in cis by transcriptional interference. Cell 127, 1209-1221.

Nakayama, T., Nishioka, K., Dong, Y.-X., Shimojima, T. and Hirose, S. (2007). Drosophila GAGA factor directs histone H3.3 replacement that prevents the heterochromatin spreading. Genes Dev. 21, 552-561.

Hanai, K., Furuhashi, H., Yamamoto, T., Akasaka, K. and Hirose, S. (2008). RSF governs silent chromatin formation via histone H2Av replacement. PLoS Genetics 4(2) : e1000011.