How epigenetic states defined by chromatin organization are inherited remains one of the most enigmatic, yet fundamental questions in the field of chromatin research. Accumulated data show that dysregulation of this process is linked to various diseases, including cancer and premature aging. The long-term goals of the lab's research are aimed at addressing: 1) how epigenetic information, defined by chromatin structures, is inherited during mitotic cell division; 2)how this process is involved in maintaining genome integrity; and 3) how this process goes awry in human disease. Specifically, using both yeast and mammalian cells, we will determine how nucleosomes, the basic repeating units of chromatin, are disassembled/reassembled in a process coupled to DNA replication and how DNA replication-coupled (RC) nucleosome dynamics impacts epigenetic silencing. These studies will utilize combinatorial tools including biochemistry, genetics and genome-wide approaches to dissect the detailed mechanisms driving this crucial process. Answers to these questions will not only have significant scientific value, but will also likely lead to the discovery of novel drug targets for the treatment of diseases caused by epigenetic alterations.
本实验室主要研究方向为表观遗传信息的传递（Epigenetic Inheritance)
在细胞分裂过程中，伴随着DNA的复制，高度折叠的染色质结构所携带的表观遗传信息如何稳定的从细胞传递到细胞，从而维持其基因表达模式的一致性和基因组的稳定性，一直是生命科学领域的一个谜。大量的临床数据和基础研究表明，该过程的失调可能导致疾病的发生例如肿瘤、早衰以及神经退行性疾病等。因此，探索在细胞分裂过程中，染色质结构所携带的表观遗传信息是如何稳定传递的至关重要。
染色质的最基本组成单位是核小体。核小体由一段147 bp的DNA片断缠绕一个组蛋白八聚体(包括各两个拷贝的组蛋白H2A、H2B、H3和H4)约两圈构成。串珠状的核小体进一步通过高度反复盘绕折叠，最终形成染色质。在DNA相关代谢活动中，核小体作为染色质的最基本组成单位，其组装和解组装必须被精确调控。在DNA复制过程中，复制叉前面的1-2个核小体必须被解组装以辅助DNA聚合酶的前行；而在复制叉后面，新的核小体必须被迅速组装从而恢复染色质的结构，这个过程被称为DNA复制耦联的核小体组装（DNA replication coupled nucleosome assembly)，是表观遗传信息稳定传递的最基本也是最关键的一步。
本实验室主要以酵母为模式，一方面应用生物化学方法，结合免疫共沉淀和质谱等鉴定技术，分离和鉴定蛋白质复合物，另一方面运用经典的酵母遗传分析，寻找调控表观遗传信息传递的新因子；同时，利用体内、外功能分析体系，结合ChIP-Seq和nucleosome positioning等基因组水平方法解析表观遗传信息传递机制，致力于探索表观遗传学的基础理论。实验室将以DNA复制耦联的核小体组装为锲入点，从染色质组装的角度， 揭示：1、在细胞分裂过程中，染色质所携带的表观遗传信息是如何被稳定传递的；2、表观遗传信息的稳定遗传如何调控基因组的稳定性；3、表观遗传调控网络在疾病发生过程中的作用机理。
代表性论文
1. Dan Su#, Qi Hu#, Qing Li#, James R. Thompson, Gaofeng Cui, Ahmed Fazly, Brian A. Davies, Maria Victoria Botuyan, Zhiguo Zhang & Georges Mer , Structural basis for recognition of H3K56-acetylated histone H3–H4 by the chaperone Rtt106 , Nature , 2012 , doi:10.1038/nature10861 , [Full Text] , (# equal contribution)
2. Qing Li and Zhiguo Zhang* , Linking DNA replication to heterochromatin silencing and epigenetic inheritance , Acta Biochimica et Biophysica Sinica , 2012 , 44 (1): 3-13 , [Full Text] , Review
3. Qing Li＃, Rebecca Burgess＃, and Zhiguo Zhang* , All roads lead to chromatin: Multiple pathways for histone deposition , Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms , 2011 , In Press, Corrected Proof. , [Full Text] , (# equal contribution) Review
4. Junhong Han, Qing Li, Laura McCullough, Tim Formosa and Zhiguo Zhang* , Ubiquitylation of FACT by the Cullin-E3 ligase Rtt101 connects FACT to DNA replication , Genes & Development , 2010 , 24:1485-1490 , [Full Text]
5. Qing Li, Ahmed Fazly, Hui Zhou, Shengbing Huang, Zhiguo Zhang* and Bruce Stillman* , The Elongator complex interacts with PCNA and modulates transcriptional silencing and sensitivity to DNA damage agents , PLoS Genetics , 2009 , 5 (10): e1000684 , [Full Text]
6. Qing Li＃, Hui Zhou＃, Hugo Wurtele, Brian Davies, Bruce Horazdovasky, Alain Verreault* and Zhiguo Zhang* , Acetylation of Histone H3 lysine 56 regulates CAF-1 dependent nucleosome assembly , Cell , 2008 , 134: 244-255 , [Full Text] , (# equal contribution) Previewed in the same issue. Highlighted in Nature Reviews Molecular Cell Biology September 2008
7. Pei Han＃, Qing Li＃ and Yuxian Zhu* , Mutation of Arabidopsis BARD1 Causes Meristem Defects by Failing to Confine WUSCHEL Expression to the Organizing Center , The Plant cell , 2008 , 20: 1482-93 , [Full Text] , (# equal contribution).
8. Qing Li, Baichen Wang, Yu Xu and Yuxian Zhu* , Systematic studies of 12S seed storage protein accumulation and degradation patterns during Arabidopsis seed maturation and early seedling germination stages , Journal of Biochemistry and Molecular Biology , 2007 , 40: 373~381
9. Qing Li, Jianxun Feng, Pei Han and Yuxian Zhu* , Parental RNA is significantly degraded during Arabidopsis seed germination , Journal of Integrative Plant Biology , 2006 , 48 (1): 114-120
10. Dayong Wang, Yunjian Xu, Qing Li, Xuemei Hao, Keming Cui, Fangzhen Sun and Yuxian Zhu , Transgenic expression of a putative calcium transporter affects the time of Arabidopsis flowering , The Plant Journal , 2003 , 33: 285-292
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