Combinatorial regulation of hepatic cytoplasmic signaling and nuclear transcriptional events by the OGT/REV-ERBα complex.
Combinatorial regulation of hepatic cytoplasmic signaling and nuclear transcriptional events by the OGT/REV-ERBα complex.
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DOI：
10.1073/pnas.1805397115
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发表时间：
2018-11-20
影响因子：
11.1
通讯作者：
Lefebvre P
中科院分区：
文献类型：
--
作者：
Berthier A;Vinod M;Porez G;Steenackers A;Alexandre J;Yamakawa N;Gheeraert C;Ploton M;Maréchal X;Dubois-Chevalier J;Hovasse A;Schaeffer-Reiss C;Cianférani S;Rolando C;Bray F;Duez H;Eeckhoute J;Lefebvre T;Staels B;Lefebvre P
使用interactomic方法，我们已经确定了核受体REV-ERBα作为O-GlcNAc转移酶（OGT）蛋白伴侣。REV-ERBα保护胞浆OGT免受蛋白酶体降解，促进胞浆和核蛋白O-GlcNAc化，而REV-ERα配体降低胞浆OGT活性。因此，REV-ERBα通过OGT、协调信号转导、表观基因组编程和肝脏中的转录反应发挥多效性活性。核受体REV-ERBα通过在基因组调控区使转录共调节因子成核，将生物钟与肝脏葡萄糖和脂质代谢整合在一起。一种相互作用的方法将O-GlcNAc转移酶（OGT）鉴定为REV-ERBα−相互作用蛋白。REV-ERBα通过保护细胞质OGT免受蛋白酶体降解并促进细胞核中的OGT活性，周期性地增加多种细胞质和细胞核蛋白的O-GlcNAc化，这是其节律性调节表达的功能，而REV-ERBα配体主要影响细胞质OGT活性。我们通过显示REV-ERBα控制细胞质蛋白激酶AKT（胰岛素信号传导中的重要中继）和细胞核中10/11易位（泰特）酶的OGT依赖性活性来说明这一发现。AKT磷酸化与REV-ERBα表达呈负相关。REV-ERBα增强了REV-ERBα基因组结合位点附近的泰特活性和DNA羟甲基化胞嘧啶（5 hmC）水平。作为一个例子，我们发现REV-ERBα/OGT复合物通过首先抑制AKT磷酸化并通过表观基因组引发Srebf 1启动子对胰岛素的进一步快速反应来调节整个禁食/进食期间SREBP-1c基因的表达。结论：REV-ERBα调节细胞质和细胞核OGT控制的过程，这些过程整合在肝脏SREBF 1基因座，以控制时间和营养调节的脂肪生成SREBP-1c转录物的基础和胰岛素诱导表达。
Using an interactomic approach, we have identified the nuclear receptor REV-ERBα as a O-GlcNAc transferase (OGT) protein partner. REV-ERBα protects cytoplasmic OGT from proteasomal degradation and facilitates cytosolic and nuclear protein O-GlcNAcylation while REV-ERα ligands decreased cytoplasmic OGT activity. REV-ERBα thus exerts pleiotropic activities through OGT, coordinating signal transduction, epigenomic programming, and transcriptional response in the liver. The nuclear receptor REV-ERBα integrates the circadian clock with hepatic glucose and lipid metabolism by nucleating transcriptional comodulators at genomic regulatory regions. An interactomic approach identified O-GlcNAc transferase (OGT) as a REV-ERBα−interacting protein. By shielding cytoplasmic OGT from proteasomal degradation and favoring OGT activity in the nucleus, REV-ERBα cyclically increased O-GlcNAcylation of multiple cytoplasmic and nuclear proteins as a function of its rhythmically regulated expression, while REV-ERBα ligands mostly affected cytoplasmic OGT activity. We illustrate this finding by showing that REV-ERBα controls OGT-dependent activities of the cytoplasmic protein kinase AKT, an essential relay in insulin signaling, and of ten-of-eleven translocation (TET) enzymes in the nucleus. AKT phosphorylation was inversely correlated to REV-ERBα expression. REV-ERBα enhanced TET activity and DNA hydroxymethylated cytosine (5hmC) levels in the vicinity of REV-ERBα genomic binding sites. As an example, we show that the REV-ERBα/OGT complex modulates SREBP-1c gene expression throughout the fasting/feeding periods by first repressing AKT phosphorylation and by epigenomically priming the Srebf1 promoter for a further rapid response to insulin. Conclusion: REV-ERBα regulates cytoplasmic and nuclear OGT-controlled processes that integrate at the hepatic SREBF1 locus to control basal and insulin-induced expression of the temporally and nutritionally regulated lipogenic SREBP-1c transcript.
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影响因子：
4
作者：
Grant, Daniel;Yin, Lei;Zuercher, William J.
通讯作者：
Zuercher, William J.
DOI：
10.14440/jbm.2018.244
发表时间：
2018-01-01
期刊：
Journal of Biological Methods
影响因子：
--
作者：
Hering, Yuliya;Berthier, Alexandre;Gul, Sheraz
通讯作者：
Gul, Sheraz
影响因子：
9.8
作者：
Jouffe C;Cretenet G;Symul L;Martin E;Atger F;Naef F;Gachon F
通讯作者：
Gachon F
DOI：
10.1073/pnas.95.11.5987
发表时间：
1998-05-26
影响因子：
11.1
作者：
Horton, JD;Bashmakov, Y;Shimano, H
通讯作者：
Shimano, H
DOI：
10.1126/science.1198125
发表时间：
2011-03-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Feng D;Liu T;Sun Z;Bugge A;Mullican SE;Alenghat T;Liu XS;Lazar MA
通讯作者：
Lazar MA