Cryo-EM structure of an epigenetic regulator in complex with the nucle…

[BK21 Plus Seminar]

▶Subject: Cryo-EM structure of an epigenetic regulator in complex with the nucleosome

▶Speaker: Uhn-Soo Cho, Ph.D. (University of Michigan, Department of Biological Chemistry)

▶Date: 4:30PM/May 23(Thur.)/2019

▶Place: Auditorium(1F), Postech Biotech Center

​▶Abctract
Polycomb and Trithorax(TrxG) groups are two protein families that repress and activate the same developmental genes, respectively. Mixed Lineage Leukemia (MLL), belonging to TrxG, is a histone H3 Lys4 methyltransferase whose function is associated with gene activation. The methyltransferase activity of MLL achieves through complex formation of the C-terminal Set domain of MLL together with RbBP5, WDR5, Ash2L, and DPY30. Despite three decades of research, the molecular mechanism of nucleosome recognition and substrate specificity mediated by the MLL complex has not been addressed. Here, we report the cryo-electron microscopy (cryo-EM) structure of the human MLL1 core complex bound to nucleosome. The structure reveals that the MLL1 core complex docks at the edge of the nucleosome using two anchoring points, RbBP5 and Ash2L. RbBP5 uses two evolutionarily unique insertion and anchoring loops to recognize the histone H4 tail and nucleosomal DNA simultaneously. Two intrinsically disordered regions (IDRs) of Ash2L provide the second binding site to nucleosomal DNA. As a result, the catalytic MLL1Set domain positions at the nucleosomal dyad, which allows both histone H3 Lys4 residues can access to the active site in a similar probability. Taken together, the cryo-EM structure of the MLL1 core complex bound to nucleosome provides the mechanistic explanation of nucleosome recognition and substrate specificity.

▶Inquiry: Prof. Taekyung Kim (279-2293)

 * This seminar will be given in English.
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