Details

Autor(en) / Beteiligte

• Hsu, Peter L.
• Shi, Hui
• Leonen, Calvin
• Kang, Jianming
• Chatterjee, Champak
• Zheng, Ning

Titel

Structural Basis of H2B Ubiquitination-Dependent H3K4 Methylation by COMPASS

Ist Teil von

• Molecular cell, 2019-12, Vol.76 (5), p.712-723.e4

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Cryo-EM structures of COMPASS bound to a H2B-ubiquitinated and unmodified nucleosome•COMPASS captures nucleosomes by extensive interfacing with both histones and DNA•The Set1 ARM helix autoinhibits COMPASS upon nucleosome binding•H2Bub allosterically activates COMPASS by anchoring to the Set1 ARM helix The cryo-EM structures of the yeast COMPASS methyltransferase bound to H2Bub and unmodified nucleosomes reveal an arginine-rich motif in the catalytic subunit, whose autoinhibitory effect on the enzymatic complex is overridden by H2B-conjugated ubiquitin. The study sheds light on the mechanism of an evolutionarily conserved crosstalk between two histone modifications.