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KMID : 0624620150480120685
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BMB Reports
2015 Volume.48 No. 12 p.685 ~ p.690
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Identification of small molecules that inhibit the histone chaperone Asf1 and its chromatin function
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Seol Ja-Hwan
Song Tae-Yang
Oh Se-Eun
Jo Chan-Hee
Choi Ah-Reum
Kim Byung-Ho
Park Jin-Young
Hong Su-Ji
Song Il-Rang
Jung Kwan-Young
Yang Jae-Hyun
Park Hwang-Seo
Ahn Jin-Hyun
Han Jeung-Whan
Cho Eun-Jung
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Abstract
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The eukaryotic genome is packed into chromatin, which is important for the genomic integrity and gene regulation. Chromatin structures are maintained through assembly and disassembly of nucleosomes catalyzed by histone chaperones. Asf1 (anti-silencing function 1) is a highly conserved histone chaperone that mediates histone transfer on/off DNA and promotes histone H3 lysine 56 acetylation at globular core domain of histone H3. To elucidate the role of Asf1 in the modulation of chromatin structure, we screened and identified small molecules that inhibit Asf1 and H3K56 acetylation without affecting other histone modifications. These pyrimidine- 2,4,6-trione derivative molecules inhibited the nucleosome assembly mediated by Asf1 in vitro, and reduced the H3K56 acetylation in HeLa cells. Furthermore, production of HSV viral particles was reduced by these compounds. As Asf1 is implicated in genome integrity, cell proliferation, and cancer, current Asf1 inhibitor molecules may offer an opportunity for the therapeutic development for treatment of diseases.
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KEYWORD
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Asf1, Epigenetic Regulation, Histone acetylation, Histone chaperone, Histone H3
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