Moshkin Yuri M, Kan Tsung Wai, Goodfellow Henry, Bezstarosti Karel, Maeda Robert K, Pilyugin Maxim, Karch Francois, Bray Sarah J, Demmers Jeroen A A, Verrijzer C Peter
Department of Biochemistry, Center for Biomedical Genetics, Erasmus University Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
Mol Cell. 2009 Sep 24;35(6):782-93. doi: 10.1016/j.molcel.2009.07.020.
Histone chaperones are involved in a variety of chromatin transactions. By a proteomics survey, we identified the interaction networks of histone chaperones ASF1, CAF1, HIRA, and NAP1. Here, we analyzed the cooperation of H3/H4 chaperone ASF1 and H2A/H2B chaperone NAP1 with two closely related silencing complexes: LAF and RLAF. NAP1 binds RPD3 and LID-associated factors (RLAF) comprising histone deacetylase RPD3, histone H3K4 demethylase LID/KDM5, SIN3A, PF1, EMSY, and MRG15. ASF1 binds LAF, a similar complex lacking RPD3. ASF1 and NAP1 link, respectively, LAF and RLAF to the DNA-binding Su(H)/Hairless complex, which targets the E(spl) NOTCH-regulated genes. ASF1 facilitates gene-selective removal of the H3K4me3 mark by LAF but has no effect on H3 deacetylation. NAP1 directs high nucleosome density near E(spl) control elements and mediates both H3 deacetylation and H3K4me3 demethylation by RLAF. We conclude that histone chaperones ASF1 and NAP1 differentially modulate local chromatin structure during gene-selective silencing.
组蛋白伴侣参与多种染色质相关活动。通过蛋白质组学研究，我们确定了组蛋白伴侣ASF1、CAF1、HIRA和NAP1的相互作用网络。在此，我们分析了H3/H4伴侣ASF1和H2A/H2B伴侣NAP1与两种密切相关的沉默复合物：LAF和RLAF的合作情况。NAP1与RPD3以及包含组蛋白去乙酰化酶RPD3、组蛋白H3K4去甲基化酶LID/KDM5、SIN3A、PF1、EMSY和MRG15的LID相关因子（RLAF）结合。ASF1与LAF结合，LAF是一种缺乏RPD3的类似复合物。ASF1和NAP1分别将LAF和RLAF与DNA结合的Su(H)/无毛复合物相连，该复合物靶向E(spl) NOTCH调控的基因。ASF1促进LAF对H3K4me3标记的基因选择性去除，但对H3去乙酰化没有影响。NAP1引导E(spl)调控元件附近的高核小体密度，并介导RLAF对H3的去乙酰化和H3K4me3的去甲基化。我们得出结论，组蛋白伴侣ASF1和NAP1在基因选择性沉默过程中对局部染色质结构进行差异调节。
