LPS-induced neuroinflammation induces changes in the transcriptional profile of members of the CoRest repressive complex in the hippocampus.

IF 2.6 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Liebert Bernardes Carvalho, Kusai Baroudi, Cleiton França, Arila Adorno Scorzafava Gonçalves, Maria Martha Bernadi, Rodrigo Augusto Foganholi da Silva
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引用次数: 0

Abstract

The action of Corepressor for Element Silencing Transcription Factor 1 (CoREST) is primarily related to neural fate decisions. However, the molecular mechanisms linking neuroinflammation to the histone modifying complex remain unclear. CoREST is a hub for several cofactors that play important roles in epigenetic remodeling and transcriptional regulation. It allows us to question their functions during the inflammatory response in the Central Nervous System. The impact of LPS-induced neuroinflammation on the transcriptional epigenetic control of members with CoRest repressive complex in the hippocampus was investigated. Characterizing the basal transcriptional profile in the hippocampus of members with CoREST repressive complex showed that the Rcor3 is the most expressed gene, and the Rcor2 is the least expressed one. It was also demonstrated that the levels of Lsd1, CoREST1 (Rcor1), and CoREST2 (Rcor2) transcripts increased in the hippocampus after LPS i.p. administration, while for CoREST3 (Rcor3), no significant difference was observed. A significant increase was noticed in the percentages of the 5-meC mark (Hypermethylation) for the Rcor1 and Lsd1 genes with a positive Pearson correlation between methylation and expression. However, the correlation was directly proportional, ruling out DNA methylation as the main mechanism in transcriptional control.

LPS诱导的神经炎症会诱导海马中CoRest抑制复合体成员的转录谱发生变化。
元素沉默转录因子 1 核心抑制因子(CoREST)的作用主要与神经命运的决定有关。然而,神经炎症与组蛋白修饰复合物之间的分子机制仍不清楚。CoREST是在表观遗传重塑和转录调控中发挥重要作用的几种辅助因子的枢纽。通过它,我们可以探究它们在中枢神经系统炎症反应中的功能。我们研究了 LPS 诱导的神经炎症对海马中 CoRest 抑制复合体成员转录表观遗传调控的影响。对CoREST抑制复合体成员海马体的基础转录特征进行的分析表明,Rcor3是表达最多的基因,而Rcor2是表达最少的基因。研究还表明,在注射 LPS 后,海马中 Lsd1、CoREST1(Rcor1)和 CoREST2(Rcor2)转录本的水平升高,而 CoREST3(Rcor3)则无明显差异。在 Rcor1 和 Lsd1 基因中,5-meC 标记(高甲基化)的百分比明显增加,甲基化与表达之间呈正的皮尔逊相关性。不过,这种相关性是正比例关系,排除了 DNA 甲基化是转录控制主要机制的可能性。
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来源期刊
Molecular Biology Reports
Molecular Biology Reports 生物-生化与分子生物学
CiteScore
5.00
自引率
0.00%
发文量
1048
审稿时长
5.6 months
期刊介绍: Molecular Biology Reports publishes original research papers and review articles that demonstrate novel molecular and cellular findings in both eukaryotes (animals, plants, algae, funghi) and prokaryotes (bacteria and archaea).The journal publishes results of both fundamental and translational research as well as new techniques that advance experimental progress in the field and presents original research papers, short communications and (mini-) reviews.
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