Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-56806
Nat Commun January 1, 2019; 10 (1): 5540.

Cryo-EM structure of the human MLL1 core complex bound to the nucleosome.

Park SH , Ayoub A , Lee YT , Xu J , Kim H , Zheng W , Zhang B , Sha L , An S , Zhang Y , Cianfrocco MA , Su M , Dou Y , Cho US .


Abstract
Mixed lineage leukemia (MLL) family histone methyltransferases 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 nucleosome core particles (NCPs) remain unclear. Here we report the single-particle cryo-electron microscopy (cryo-EM) structure of the NCP-bound human MLL1 core complex. We show that the MLL1 core complex anchors to the NCP via the conserved RbBP5 and ASH2L, which interact extensively with nucleosomal DNA and the surface close to the N-terminal tail of histone H4. Concurrent interactions of RbBP5 and ASH2L with the NCP uniquely align the catalytic MLL1SET domain at the nucleosome dyad, thereby facilitating symmetrical access to both H3K4 substrates within the NCP. Our study sheds light on how the MLL1 complex engages chromatin and how chromatin binding promotes MLL1 tri-methylation activity.

PubMed ID: 31804488
PMC ID: PMC6895043
Article link: Nat Commun
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: ash2l dot1l dpy30 kmt2a rbbp5 wdr5


Article Images: [+] show captions
References [+] :
Afonine, Real-space refinement in PHENIX for cryo-EM and crystallography. 2018, Pubmed