The assembly of mammalian SWI/SNF chromatin remodeling complexes is regulated by lysine-methylation dependent proteolysis.
The assembly of mammalian SWI/SNF chromatin remodeling complexes is regulated by lysine-methylation dependent proteolysis.
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DOI：
10.1038/s41467-022-34348-9
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发表时间：
2022-11-05
影响因子：
16.6
通讯作者：
Zhang, Hui
中科院分区：
文献类型：
--
作者：
Guo, Pengfei;Hoang, Nam;Sanchez, Joseph;Zhang, Elaine H.;Rajawasam, Keshari;Trinidad, Kristiana;Sun, Hong;Zhang, Hui
哺乳动物SWI/SNF染色质重塑复合物的组装是发育编程的，SWI/SNF亚基的缺失/突变通过蛋白水解改变其他组分的水平，从而导致癌症。在这里，我们表明，小鼠Lsd 1/Kdm 1a缺失导致急剧溶解的SWI/SNF复合物和LSD 1去甲基化的SMARCC 1和SMARCC 2中的甲基化赖氨酸残基，以保持SWI/SNF复合物的结构完整性。甲基化SMARCC 1/SMARCC 2被L3 MBTL 3和CRL 4DCAF 5泛素连接酶复合物靶向蛋白水解。我们确定SMARCC 1是LSD 1和L3 MBTL 3维持胚胎干细胞多能性和自我更新的关键靶点。L3 MBTL 3还调节由SWI/SNF亚基的缺失诱导的SMARCC 1/SMARCC 2蛋白水解。一致地，小鼠L3 mbtl 3缺失导致SWI/SNF组分的显著积累，与胚胎致死相关。我们的研究表明，SWI/SNF复合物的组装/拆卸是动态控制的赖氨酸甲基化依赖的蛋白水解机制，以保持SWI/SNF复合物的完整性。在这里，作者表明哺乳动物SWI/SNF复合物的组装/拆卸是由赖氨酸甲基化机制动态调节的，该机制涉及脱甲基酶LSD 1和甲基赖氨酸阅读器L3 MBTL 3，该阅读器识别SMARCC 1和SMARCC 2中的SET 7甲基化赖氨酸，以靶向它们进行CRL 4泛素连接酶介导的蛋白水解。
The assembly of mammalian SWI/SNF chromatin remodeling complexes is developmentally programed, and loss/mutations of SWI/SNF subunits alter the levels of other components through proteolysis, causing cancers. Here, we show that mouse Lsd1/Kdm1a deletion causes dramatic dissolution of SWI/SNF complexes and that LSD1 demethylates the methylated lysine residues in SMARCC1 and SMARCC2 to preserve the structural integrity of SWI/SNF complexes. The methylated SMARCC1/SMARCC2 are targeted for proteolysis by L3MBTL3 and the CRL4DCAF5 ubiquitin ligase complex. We identify SMARCC1 as the critical target of LSD1 and L3MBTL3 to maintain the pluripotency and self-renewal of embryonic stem cells. L3MBTL3 also regulates SMARCC1/SMARCC2 proteolysis induced by the loss of SWI/SNF subunits. Consistently, mouse L3mbtl3 deletion causes striking accumulation of SWI/SNF components, associated with embryonic lethality. Our studies reveal that the assembly/disassembly of SWI/SNF complexes is dynamically controlled by a lysine-methylation dependent proteolytic mechanism to maintain the integrity of the SWI/SNF complexes. Here the authors show the assembly/disassembly of mammalian SWI/SNF complexes is dynamically regulated by a lysine methylation mechanism involving the demethylase LSD1 and the methyl-lysine reader L3MBTL3, which recognizes SET7-methylated lysines in SMARCC1 and SMARCC2 to target them for CRL4 ubiquitin ligase-mediated proteolysis.
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影响因子：
28.2
作者：
Kar SP;Beesley J;Amin Al Olama A;Michailidou K;Tyrer J;Kote-Jarai Z;Lawrenson K;Lindstrom S;Ramus SJ;Thompson DJ;ABCTB Investigators;Kibel AS;Dansonka-Mieszkowska A;Michael A;Dieffenbach AK;Gentry-Maharaj A;Whittemore AS;Wolk A;Monteiro A;Peixoto A;Kierzek A;Cox A;Rudolph A;Gonzalez-Neira A;Wu AH;Lindblom A;Swerdlow A;AOCS Study Group & Australian Cancer Study (Ovarian Cancer);APCB BioResource;Ziogas A;Ekici AB;Burwinkel B;Karlan BY;Nordestgaard BG;Blomqvist C;Phelan C;McLean C;Pearce CL;Vachon C;Cybulski C;Slavov C;Stegmaier C;Maier C;Ambrosone CB;Høgdall CK;Teerlink CC;Kang D;Tessier DC;Schaid DJ;Stram DO;Cramer DW;Neal DE;Eccles D;Flesch-Janys D;Edwards DR;Wokozorczyk D;Levine DA;Yannoukakos D;Sawyer EJ;Bandera EV;Poole EM;Goode EL;Khusnutdinova E;Høgdall E;Song F;Bruinsma F;Heitz F;Modugno F;Hamdy FC;Wiklund F;Giles GG;Olsson H;Wildiers H;Ulmer HU;Pandha H;Risch HA;Darabi H;Salvesen HB;Nevanlinna H;Gronberg H;Brenner H;Brauch H;Anton-Culver H;Song H;Lim HY;McNeish I;Campbell I;Vergote I;Gronwald J;Lubiński J;Stanford JL;Benítez J;Doherty JA;Permuth JB;Chang-Claude J;Donovan JL;Dennis J;Schildkraut JM;Schleutker J;Hopper JL;Kupryjanczyk J;Park JY;Figueroa J;Clements JA;Knight JA;Peto J;Cunningham JM;Pow-Sang J;Batra J;Czene K;Lu KH;Herkommer K;Khaw KT;kConFab Investigators;Matsuo K;Muir K;Offitt K;Chen K;Moysich KB;Aittomäki K;Odunsi K;Kiemeney LA;Massuger LF;Fitzgerald LM;Cook LS;Cannon-Albright L;Hooning MJ;Pike MC;Bolla MK;Luedeke M;Teixeira MR;Goodman MT;Schmidt MK;Riggan M;Aly M;Rossing MA;Beckmann MW;Moisse M;Sanderson M;Southey MC;Jones M;Lush M;Hildebrandt MA;Hou MF;Schoemaker MJ;Garcia-Closas M;Bogdanova N;Rahman N;NBCS Investigators;Le ND;Orr N;Wentzensen N;Pashayan N;Peterlongo P;Guénel P;Brennan P;Paulo P;Webb PM;Broberg P;Fasching PA;Devilee P;Wang Q;Cai Q;Li Q;Kaneva R;Butzow R;Kopperud RK;Schmutzler RK;Stephenson RA;MacInnis RJ;Hoover RN;Winqvist R;Ness R;Milne RL;Travis RC;Benlloch S;Olson SH;McDonnell SK;Tworoger SS;Maia S;Berndt S;Lee SC;Teo SH;Thibodeau SN;Bojesen SE;Gapstur SM;Kjær SK;Pejovic T;Tammela TL;GENICA Network;PRACTICAL consortium;Dörk T;Brüning T;Wahlfors T;Key TJ;Edwards TL;Menon U;Hamann U;Mitev V;Kosma VM;Setiawan VW;Kristensen V;Arndt V;Vogel W;Zheng W;Sieh W;Blot WJ;Kluzniak W;Shu XO;Gao YT;Schumacher F;Freedman ML;Berchuck A;Dunning AM;Simard J;Haiman CA;Spurdle A;Sellers TA;Hunter DJ;Henderson BE;Kraft P;Chanock SJ;Couch FJ;Hall P;Gayther SA;Easton DF;Chenevix-Trench G;Eeles R;Pharoah PD;Lambrechts D
通讯作者：
Lambrechts D
哺乳动物SWI/SNF复合物的蛋白质组学和生物信息学分析确定了在人类恶性肿瘤中的广泛作用。
影响因子：
30.8
作者：
Kadoch, Cigall;Hargreaves, Diana C.;Hodges, Courtney;Elias, Laura;Ho, Lena;Ranish, Jeff;Crabtree, Gerald R.
通讯作者：
Crabtree, Gerald R.
DOI：
10.18632/aging.100471
发表时间：
2012-07
期刊：
Aging
影响因子：
--
作者：
Calnan DR;Webb AE;White JL;Stowe TR;Goswami T;Shi X;Espejo A;Bedford MT;Gozani O;Gygi SP;Brunet A
通讯作者：
Brunet A
影响因子：
11.4
作者：
Arai, S;Miyazaki, T
通讯作者：
Miyazaki, T
影响因子：
5.3
作者：
Chen, JG;Archer, TK
通讯作者：
Archer, TK