The Team of NKU Newly Released the Connection between Gene Regulation and Human Diseases 2018.10.01

Model diagram of Paf1 complex assembly, histone modifications and coordinated RNA polymerase II function

How does the gene regulation involve in development and human diseased? This is a topic that scientists from all over the world strive for revelation. Recently, the team led by Professor Jiafu Long, Nankai University’s College of Life Sciences and the State Key Laboratory of Medicinal Chemical Biology, revealed the mystery of polymerase-associated factor 1 (Paf1) complex assembly and functional regulation, an important protein complex that affects gene expression and regulation. It lays a molecular foundation for the treatment and drug development of related tumors. On September 18th, the related paper was published online in the internationally renowned academic journal Nature Communications.

After years of painstaking research, Long’s team analyzed the crystal structure of the human and yeast source Paf1-Ctr9 subcomplex with an interdisciplinary method combining biochemistry, structural biology and cell biology. The study shows that the Paf1-Ctr9 sub complex plays vital roles in the assembly of the entire Paf1 complex. The related work revealed the molecular basis for gene mutations of Paf1 that leads to relevant tumors, and the important role of the sub-complex in histone methylation modification and yeast vitality.

This is another important progress by the Long’s team o in the field of Paf1 complex assembly and functional regulation after their publication on the structural basis of Paf1 and Leo1 subcomplex assembly and histone binding in Nucleic Acids Research in 2013. Prof. Jiafu Long and associate professor Hao Zhou are the co-corresponding authors of the paper. Doctoral students Ying Xie and Minying Zheng are the co-first authors of the paper. Professor Jiawei Wang of Tsinghua University offered advice for the research work in structural analysis. Doctoral student Chu Xinlei from Tianjin Medical University Cancer Hospital participated in some biochemical experiments.

Long’s team has committed to the study on the structure and function of epigenetic regulatory proteins during gene expression and regulation and their connection with human diseases. Recently, the team has elucidated the assembly pattern among the subunits (six subunits) of the histone acetylation-modifying enzyme Elongator complex (PNAS, 2015; Structure, 2015; JBC, 2012) and the molecular mechanism of Angiomotin mediating Merlin in order to activate Hippo signal pathway in the upstream related signal pathway during gene expression regulation (Cell Res., 2015). It has also conducted a preliminary research on the assembly pattern between the two subunits in the Paf1 complex (six subunits) (Nucleic Acids Res., 2013) and clarifies the molecular mechanism of the important protein SATB1 involved in chromosomal allosterism in local and long-range regulation of gene expression (Nucleic Acids Res., 2012; JBC, 2014).

Link to: https://www.nature.com/articles/s41467-018-06237-7

Source: Nankai News

Written by Junhui Wu

Edited by Kuqing Li and Ruoyan Yan



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