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组蛋白 H4 乙酰化差异调节成年少突胶质前体细胞的增殖。

Histone H4 acetylation differentially modulates proliferation in adult oligodendrocyte progenitors.

机构信息

Neuroscience Initiative, Advanced Science Research Center at the City University of New York, New York, NY, USA.

Graduate Program in Biochemistry, The Graduate Center of The City University of New York, New York, NY, USA.

出版信息

J Cell Biol. 2024 Nov 4;223(11). doi: 10.1083/jcb.202308064. Epub 2024 Aug 12.

DOI:10.1083/jcb.202308064
PMID:39133301
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11318668/
Abstract

Adult oligodendrocyte progenitors (aOPCs) generate myelinating oligodendrocytes like neonatal progenitors (nOPCs), and they also display unique functional features. Here, using unbiased histone proteomics analysis and ChIP sequencing analysis of PDGFRα+ OPCs sorted from neonatal and adult Pdgfra-H2B-EGFP reporter mice, we identify the activating H4K8ac histone mark as enriched in the aOPCs. We detect increased occupancy of the H4K8ac activating mark at chromatin locations corresponding to genes related to the progenitor state (e.g., Hes5, Gpr17), metabolic processes (e.g., Txnip, Ptdgs), and myelin components (e.g., Cnp, Mog). aOPCs showed higher levels of transcripts related to lipid metabolism and myelin, and lower levels of transcripts related to cell cycle and proliferation compared with nOPCs. In addition, pharmacological inhibition of histone acetylation decreased the expression of the H4K8ac target genes in aOPCs and decreased their proliferation. Overall, this study identifies acetylation of the histone H4K8 as a regulator of the proliferative capacity of aOPCs.

摘要

成体少突胶质前体细胞（aOPC）可像新生前体细胞（nOPC）一样生成髓鞘少突胶质细胞，并且还具有独特的功能特征。在这里，我们使用无偏蛋白组学分析和 PDGFRα+OPC 的 ChIP 测序分析，这些 OPC 是从小鼠的新生和成年 Pdgfra-H2B-EGFP 报告基因中分离出来的，我们发现激活的 H4K8ac 组蛋白标记在 aOPC 中富集。我们检测到在与祖细胞状态（例如 Hes5、Gpr17）、代谢过程（例如 Txnip、Ptdgs）和髓鞘成分（例如 Cnp、Mog）相关的基因的染色质位置上，H4K8ac 激活标记的占有率增加。与 nOPC 相比，aOPC 显示出与脂质代谢和髓鞘相关的转录物水平较高，而与细胞周期和增殖相关的转录物水平较低。此外，组蛋白乙酰化的药理学抑制降低了 aOPC 中 H4K8ac 靶基因的表达，并降低了它们的增殖能力。总体而言，这项研究确定了组蛋白 H4K8 的乙酰化是 aOPC 增殖能力的调节因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd2/11318668/b52d9b9f9771/JCB_202308064_FigS2.jpg
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