Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural basis of nucleosome recognition and modification by MLL methyltransferases.
Journal, issue, pages	Nature, Vol. 573, Issue 7774, Page 445-449, Year 2019
Publish date	Sep 4, 2019
Authors	Han Xue / Tonghui Yao / Mi Cao / Guanjun Zhu / Yan Li / Guiyong Yuan / Yong Chen / Ming Lei / Jing Huang /
PubMed Abstract	Methyltransferases of the mixed-lineage leukaemia (MLL) family-which include MLL1, MLL2, MLL3, MLL4, SET1A and SET1B-implement methylation of histone H3 on lysine 4 (H3K4), and have critical and ...Methyltransferases of the mixed-lineage leukaemia (MLL) family-which include MLL1, MLL2, MLL3, MLL4, SET1A and SET1B-implement methylation of histone H3 on lysine 4 (H3K4), and have critical and distinct roles in the regulation of transcription in haematopoiesis, adipogenesis and development. The C-terminal catalytic SET (Su(var.)3-9, enhancer of zeste and trithorax) domains of MLL proteins are associated with a common set of regulatory factors (WDR5, RBBP5, ASH2L and DPY30) to achieve specific activities. Current knowledge of the regulation of MLL activity is limited to the catalysis of histone H3 peptides, and how H3K4 methyl marks are deposited on nucleosomes is poorly understood. H3K4 methylation is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120ub1), a prevalent histone H2B mark that disrupts chromatin compaction and favours open chromatin structures, but the underlying mechanism remains unknown. Here we report cryo-electron microscopy structures of human MLL1 and MLL3 catalytic modules associated with nucleosome core particles that contain H2BK120ub1 or unmodified H2BK120. These structures demonstrate that the MLL1 and MLL3 complexes both make extensive contacts with the histone-fold and DNA regions of the nucleosome; this allows ease of access to the histone H3 tail, which is essential for the efficient methylation of H3K4. The H2B-conjugated ubiquitin binds directly to RBBP5, orienting the association between MLL1 or MLL3 and the nucleosome. The MLL1 and MLL3 complexes display different structural organizations at the interface between the WDR5, RBBP5 and MLL1 (or the corresponding MLL3) subunits, which accounts for the opposite roles of WDR5 in regulating the activity of the two enzymes. These findings transform our understanding of the structural basis for the regulation of MLL activity at the nucleosome level, and highlight the pivotal role of nucleosome regulation in histone-tail modification.
External links	Nature / PubMed:31485071
Methods	EM (single particle)
Resolution	3.2 - 4.5 Å
Structure data	0693 6kiw EMDB-0693, PDB-6kiw: Cryo-EM structure of human MLL3-ubNCP complex (4.0 angstrom) Method: EM (single particle) / Resolution: 4.0 Å 0694 6kix EMDB-0694, PDB-6kix: Cryo-EM structure of human MLL1-NCP complex, binding mode1 Method: EM (single particle) / Resolution: 4.1 Å 0695 6kiz EMDB-0695, PDB-6kiz: Cryo-EM structure of human MLL1-NCP complex, binding mode2 Method: EM (single particle) / Resolution: 4.5 Å 9998 6kiu EMDB-9998, PDB-6kiu: Cryo-EM structure of human MLL1-ubNCP complex (3.2 angstrom) Method: EM (single particle) / Resolution: 3.2 Å 9999 6kiv EMDB-9999, PDB-6kiv: Cryo-EM structure of human MLL1-ubNCP complex (4.0 angstrom) Method: EM (single particle) / Resolution: 4.0 Å
Chemicals	ChemComp-SAH: S-ADENOSYL-L-HOMOCYSTEINE ChemComp-ZN: Unknown entry ChemComp-LYS: LYSINE ChemComp-GLN: GLUTAMINE
Source	homo sapiens (human) xenopus laevis (African clawed frog) synthetic construct (others)
Keywords	TRANSCRIPTION/DNA / histone modification / nucleosome / MLL / TRANSCRIPTION / TRANSCRIPTION-DNA complex