[대학원 생명과학과 세미나 안내]
연사 : 조운수 교수 (University of Michigan)
연제 : Cryo-EM structure of the human MLL1 core complex bound to the nucleosome
일시 : 2020년 11월 13일 (금) 오후 5시
장소 : 온라인 화상 강의로 진행됩니다.
초청교수 : 우재성 교수
Abstract
Mixed Lineage Leukemia (MLL) family histonemethyltransferases are enzymes that deposit
histone H3 Lys4 (K4) mono-/di-/tri-methylation and regulate gene expression in mammals.
Despite extensive structural and biochemical studies, the molecular mechanisms whereby the
MLL complexes recognize histone H3K4 within nucleosomecore particles (NCPs) remain
unclear. Here, we report the single-particlecryo-electron microscopy (cryo-EM) structure of
the NCP-bound human MLL1 corecomplex. We show that the MLL1 core complex anchors
to the NCP via theconserved RbBP5 and ASH2L, which interact extensively with
nucleosomal DNA andthe surface close to the N-terminal tail of histone H4. Concurrent
interactionsof RbBP5 and ASH2L with the NCP uniquely align the catalytic
MLL1SETdomain at the nucleosome dyad, thereby facilitating symmetrical access to
bothH3K4 substrates within the NCP. Our study sheds light on how the MLL1 complex
engages chromatin and howchromatin binding promotes MLL1 tri-methylation activity.