Epigenomic priming of immune genes implicates oligodendroglia in multiple sclerosis susceptibility.
Epigenomic priming of immune genes implicates oligodendroglia in multiple sclerosis susceptibility.
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DOI：
10.1016/j.neuron.2021.12.034
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发表时间：
2022-04-06
期刊：
影响因子：
16.2
通讯作者：
Castelo-Branco, Goncalo
中科院分区：
文献类型：
--
作者：
Meijer, Mandy;Agirre, Eneritz;Kabbe, Mukund;van Tuijn, Cassandra A.;Heskol, Abeer;Zheng, Chao;Falcao, Ana Mendanha;Bartosovic, Marek;Kirby, Leslie;Calini, Daniela;Johnson, Michael R.;Corces, M. Ryan;Montine, Thomas J.;Chen, Xingqi;Chang, Howard Y.;Malhotra, Dheeraj;Castelo-Branco, Goncalo
多发性硬化症（MS）的特征是免疫细胞对少突胶质细胞（OLG）和髓鞘的靶向攻击，这被认为是MS易感性的主要驱动因素。我们发现，免疫基因表现出一个引发的染色质状态，在单一的小鼠和人类OLG在非疾病的背景下，兼容MS的免疫能力状态的过渡。我们确定BACH 1和STAT 1的转录因子参与免疫基因调控的少突胶质细胞前体细胞（OPC）。免疫基因的一个子集在OPC中呈现H3 K4 me 3/H3 K27 me 3的二价，其中Polycomb抑制导致它们在干扰素γ（IFN-γ）处理后活化增加。一些MS易感性单核苷酸多态性（SNP）与小鼠和人类OLG中的这些调控区域重叠。用IFN-γ处理小鼠OPCs导致这些位点的染色质结构重塑和相互作用基因的表达改变。因此，MS的易感性可能涉及OLG，其因此构成MS的基于免疫的疗法的新靶点。Meijer，Agirre等人表明小鼠和人少突胶质细胞在免疫基因处存在开放染色质，并且MS易感性在稳态和疾病中存在单核苷酸多态性。这些开放染色质区域的转录激活涉及转录因子如BACH 1和STAT 1以及组蛋白修饰沉积和染色质结构的变化。
Multiple sclerosis (MS) is characterized by a targeted attack on oligodendroglia (OLG) and myelin by immune cells, which are thought to be the main drivers of MS susceptibility. We found that immune genes exhibit a primed chromatin state in single mouse and human OLG in a non-disease context, compatible with transitions to immune-competent states in MS. We identified BACH1 and STAT1 as transcription factors involved in immune gene regulation in oligodendrocyte precursor cells (OPCs). A subset of immune genes presents bivalency of H3K4me3/H3K27me3 in OPCs, with Polycomb inhibition leading to their increased activation upon interferon gamma (IFN-γ) treatment. Some MS susceptibility single-nucleotide polymorphisms (SNPs) overlap with these regulatory regions in mouse and human OLG. Treatment of mouse OPCs with IFN-γ leads to chromatin architecture remodeling at these loci and altered expression of interacting genes. Thus, the susceptibility for MS may involve OLG, which therefore constitutes novel targets for immunological-based therapies for MS. Meijer, Agirre, et al. show that mouse and human oligodendroglia present open chromatin at immune genes and MS susceptibility single-nucleotide polymorphisms in homeostasis and disease. Transcriptional activation of these open chromatin regions involves transcription factors such as BACH1 and STAT1 and changes in histone modification deposition and chromatin architecture.
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影响因子：
17.1
作者：
Fard MK;van der Meer F;Sánchez P;Cantuti-Castelvetri L;Mandad S;Jäkel S;Fornasiero EF;Schmitt S;Ehrlich M;Starost L;Kuhlmann T;Sergiou C;Schultz V;Wrzos C;Brück W;Urlaub H;Dimou L;Stadelmann C;Simons M
通讯作者：
Simons M
DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
30.8
作者：
Finucane HK;Reshef YA;Anttila V;Slowikowski K;Gusev A;Byrnes A;Gazal S;Loh PR;Lareau C;Shoresh N;Genovese G;Saunders A;Macosko E;Pollack S;Brainstorm Consortium;Perry JRB;Buenrostro JD;Bernstein BE;Raychaudhuri S;McCarroll S;Neale BM;Price AL
通讯作者：
Price AL