A phosphorylation switch on RbBP5 regulates histone H3 Lys4 methylation.
A phosphorylation switch on RbBP5 regulates histone H3 Lys4 methylation.
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DOI：
10.1101/gad.254870.114
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发表时间：
2015-01-15
影响因子：
10.5
通讯作者：
Couture JF
中科院分区：
文献类型：
--
作者：
Zhang P;Chaturvedi CP;Tremblay V;Cramet M;Brunzelle JS;Skiniotis G;Brand M;Shilatifard A;Couture JF
The methyltransferase activity of MLL1 is allosterically regulated by a four-subunit complex composed of WDR5, RbBP5, Ash2L, and DPY30 (also referred to as WRAD). Zhang et al. show that in WRAD, a concave surface of the Ash2L SPRY domain binds to RbBP5. This Ash2L/RbBP5 interface is important for heterodimer formation, stimulation of MLL1 catalytic activity, and erythroid cell terminal differentiation. A phosphorylation switch on RbBP5 stimulates WRAD complex formation and significantly increases KMT2 enzyme methylation rates. The methyltransferase activity of the trithorax group (TrxG) protein MLL1 found within its COMPASS (complex associated with SET1)-like complex is allosterically regulated by a four-subunit complex composed of WDR5, RbBP5, Ash2L, and DPY30 (also referred to as WRAD). We report structural evidence showing that in WRAD, a concave surface of the Ash2L SPIa and ryanodine receptor (SPRY) domain binds to a cluster of acidic residues, referred to as the D/E box, in RbBP5. Mutational analysis shows that residues forming the Ash2L/RbBP5 interface are important for heterodimer formation, stimulation of MLL1 catalytic activity, and erythroid cell terminal differentiation. We also demonstrate that a phosphorylation switch on RbBP5 stimulates WRAD complex formation and significantly increases KMT2 (lysine [K] methyltransferase 2) enzyme methylation rates. Overall, our findings provide structural insights into the assembly of the WRAD complex and point to a novel regulatory mechanism controlling the activity of the KMT2/COMPASS family of lysine methyltransferases.
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影响因子：
5.7
作者：
Avdic, Vanja;Zhang, Pamela;Couture, Jean-Francois
通讯作者：
Couture, Jean-Francois
影响因子：
16.6
作者：
Shilatifard A
通讯作者：
Shilatifard A
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16
作者：
Cheng, Jemmie;Blum, Roy;Bowman, Christopher;Hu, Deqing;Shilatifard, Ali;Shen, Steven;Dynlacht, Brian D.
通讯作者：
Dynlacht, Brian D.