Decreased Expression of CoREST1 and CoREST2 Together with LSD1 and HDAC1/2 during Neuronal Differentiation.
Decreased Expression of CoREST1 and CoREST2 Together with LSD1 and HDAC1/2 during Neuronal Differentiation.
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在神经元分化过程中，Corest1和Corest2与LSD1和HDAC1/2的表达降低。
DOI：
10.1371/journal.pone.0131760
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Andrés ME
中科院分区：
文献类型：
--
作者：
Sáez JE;Gómez AV;Barrios ÁP;Parada GE;Galdames L;González M;Andrés ME
CoREST （CoREST1, rcor1）转录辅抑制因子与组蛋白去甲基化酶LSD1 （KDM1A）和组蛋白去乙酰化酶HDAC1/2共同形成LSD1-CoREST- hdac （LCH）转录复合物，调控基因表达。CoREST1与CoREST2 （rcor2）和CoREST3 （rcor3）同属一个家族。在神经元分化过程中，CoREST1抑制神经元基因的表达。然而，CoREST2和CoREST3在这个过程中的作用才刚刚开始显现。在这里，我们报告了所有corest及其伴侣LSD1和HDAC1/2在两种神经元分化模型中的表达：神经生长因子（NGF）诱导的PC12细胞的神经元表型，以及胚胎大鼠皮质神经元的体外成熟。在两种模型中，均观察到LSD1、HDAC1、HDAC2、CoREST1和CoREST2同时逐渐降低，但未观察到CoREST3。根据研究需要，利用现有大鼠基因组的计算机分析方法，鉴定了大鼠rcor1全长基因。这项工作还得到了对大鼠RNA-seq数据库分析的补充。分析结果表明，所有corest，包括鉴定的大鼠CoREST3的四个剪接变体，在成年组织中广泛表达。此外，RNA-seq数据库分析显示，CoREST2在成熟大脑中的表达高于CoREST1和CoREST3。成年大鼠脑的免疫荧光分析和免疫印迹显示，所有corest均存在于神经胶质细胞和神经元中。在功能伙伴关系方面，CoREST2和CoREST3与所有LSD1剪接变体相互作用。综上所述，神经元分化伴随着LCH复合物所有核心成分的表达下降，但CoREST3不伴有表达下降。LCH复合物的差异转录抑制能力及其不同成分的可变蛋白质水平的结合，应该导致神经元分化和成人大脑中精细调节的基因表达。
CoREST (CoREST1, rcor1) transcriptional corepressor together with the histone demethylase LSD1 (KDM1A) and the histone deacetylases HDAC1/2 form LSD1-CoREST-HDAC (LCH) transcriptional complexes to regulate gene expression. CoREST1 belong to a family that also comprises CoREST2 (rcor2) and CoREST3 (rcor3). CoREST1 represses the expression of neuronal genes during neuronal differentiation. However, the role of paralogs CoREST2 and CoREST3 in this process is just starting to emerge. Here, we report the expression of all CoRESTs and partners LSD1 and HDAC1/2 in two models of neuronal differentiation: Nerve-Growth-Factor (NGF)-induced neuronal phenotype of PC12 cells, and in vitro maturation of embryonic rat cortical neurons. In both models, a concomitant and gradual decrease of LSD1, HDAC1, HDAC2, CoREST1, and CoREST2, but not CoREST3 was observed. As required by the study, full-length rat rcor1 gene was identified using in silico analysis of available rat genome. The work was also complemented by the analysis of rat RNA-seq databases. The analysis showed that all CoRESTs, including the identified four splicing variants of rat CoREST3, display a wide expression in adult tissues. Moreover, the analysis of RNA-seq databases showed that CoREST2 displays a higher expression than CoREST1 and CoREST3 in the mature brain. Immunofluorescent assays and immunoblots of adult rat brain showed that all CoRESTs are present in both glia and neurons. Regarding functional partnership, CoREST2 and CoREST3 interact with all LSD1 splicing variants. In conclusion, neuronal differentiation is accompanied by decreased expression of all core components of LCH complexes, but not CoREST3. The combination of the differential transcriptional repressor capacity of LCH complexes and variable protein levels of its different components should result in a finely tuned gene expression during neuronal differentiation and in the adult brain.
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影响因子：
14.9
作者：
Flicek P;Amode MR;Barrell D;Beal K;Billis K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fitzgerald S;Gil L;Girón CG;Gordon L;Hourlier T;Hunt S;Johnson N;Juettemann T;Kähäri AK;Keenan S;Kulesha E;Martin FJ;Maurel T;McLaren WM;Murphy DN;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ruffier M;Sheppard D;Taylor K;Thormann A;Trevanion SJ;Vullo A;Wilder SP;Wilson M;Zadissa A;Aken BL;Birney E;Cunningham F;Harrow J;Herrero J;Hubbard TJ;Kinsella R;Muffato M;Parker A;Spudich G;Yates A;Zerbino DR;Searle SM
通讯作者：
Searle SM
影响因子：
64.5
作者：
Ballas, N;Grunseich, C;Mandel, G
通讯作者：
Mandel, G
影响因子：
64.8
作者：
Lee, MG;Wynder, C;Shiekhattar, R
通讯作者：
Shiekhattar, R
DOI：
10.1073/pnas.96.17.9873
发表时间：
1999-08-17
影响因子：
11.1
作者：
Andrés, ME;Burger, C;Mandel, G
通讯作者：
Mandel, G
影响因子：
16
作者：
Gomez, Andrea V.;Galleguillos, Danny;Andres, Maria Estela
通讯作者：
Andres, Maria Estela