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TitleStructural Basis of H2B Ubiquitination-Dependent H3K4 Methylation by COMPASS.
Journal, issue, pagesMol Cell, Vol. 76, Issue 5, Page 712-723.e4, Year 2019
Publish dateDec 5, 2019
AuthorsPeter L Hsu / Hui Shi / Calvin Leonen / Jianming Kang / Champak Chatterjee / Ning Zheng /
PubMed AbstractThe COMPASS (complex of proteins associated with Set1) complex represents the prototype of the SET1/MLL family of methyltransferases that controls gene transcription by H3K4 methylation (H3K4me). ...The COMPASS (complex of proteins associated with Set1) complex represents the prototype of the SET1/MLL family of methyltransferases that controls gene transcription by H3K4 methylation (H3K4me). Although H2B monoubiquitination (H2Bub) is well known as a prerequisite histone mark for COMPASS activity, how H2Bub activates COMPASS remains unclear. Here, we report the cryoelectron microscopy (cryo-EM) structures of an extended COMPASS catalytic module (CM) bound to the H2Bub and free nucleosome. The COMPASS CM clamps onto the nucleosome disk-face via an extensive interface to capture the flexible H3 N-terminal tail. The interface also sandwiches a critical Set1 arginine-rich motif (ARM) that autoinhibits COMPASS. Unexpectedly, without enhancing COMPASS-nucleosome interaction, H2Bub activates the enzymatic assembly by packing against Swd1 and alleviating the inhibitory effect of the Set1 ARM upon fastening it to the acidic patch. By delineating the spatial configuration of the COMPASS-H2Bub-nucleosome assembly, our studies establish the structural framework for understanding the long-studied H2Bub-H3K4me histone modification crosstalk.
External linksMol Cell / PubMed:31733991 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 3.7 Å
Structure data

20765

6ugm

EMDB-20765, PDB-6ugm:
Structural basis of COMPASS eCM recognition of an unmodified nucleosome
Method: EM (single particle) / Resolution: 3.7 Å

20767

6uh5

EMDB-20767, PDB-6uh5:
Structural basis of COMPASS eCM recognition of the H2Bub nucleosome
Method: EM (single particle) / Resolution: 3.5 Å

Chemicals

ChemComp-SAM:
S-ADENOSYLMETHIONINE / S-Adenosyl methionine

ChemComp-ZN:
Unknown entry

Source
  • xenopus laevis (African clawed frog)
  • kluyveromyces lactis (strain atcc 8585 / cbs 2359 / dsm 70799 / nbrc 1267 / nrrl y-1140 / wm37) (yeast)
  • synthetic construct (others)
  • homo sapiens (human)
KeywordsTRANSFERASE/STRUCTURAL PROTEIN/DNA / Complex / methyltransferase / epigenetics / chromatin / nucleosome / TRANSFERASE-STRUCTURAL PROTEIN-DNA complex

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