Stat stimulates histone H3K4 methylation via KDM5 inhibition in adult stem cells of budding tunicates.

IF 2 3区生物学 Q2 ANATOMY & MORPHOLOGY

Developmental Dynamics Pub Date : 2024-10-22 DOI:10.1002/dvdy.754

Yuri Kimura-Nagano, Kanoko Kishimoto, Satoko Sekida, Kaz Kawamura

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引用次数: 0

Abstract

Background: The branchial epithelium is one of the main tissues in which histone H3K4 trimethylation (H3K4me3) occurs in the budding tunicate, Polyandrocarpa misakiensis. It contains proliferating and undifferentiated cell aggregates at the bottom of each pharyngeal cleft, providing the nest for the adult stem cell niche. We examined the sustainable mechanism enabling epigenetic histone methylation in adult stem cells.

Results: Histone H3K4 demethylase (PmisKdm5) was not co-expressed in vivo with the transcription factor, signal transduction and activator of transcription (PmisStat) in the same cells. PmisStat mRNA, when electroporated into zooids, suppressed the gene expression of PmisKdm5 and facilitated the trimethylation of H3K4. A STAT5 inhibitor blocked the nuclear localization of PmisStat. It stimulated PmisKdm5 gene expression irrespective of PmisStat mRNA. The KDM5 inhibitor, CPI-455, stimulated H3K4me3 similarly to PmisStat mRNA. PmisStat mRNA and CPI-455 both induced the gene expression of PmisAp2 and PmisSp8, which were recently identified as budding/regeneration-related genes. When zooid tissues were treated with both CPI-455 and the STAT5 inhibitor, CPI-455 overwhelmed the effects of the STAT inhibitor on PmisAp2 and PmisSp8.

Conclusion: PmisStat is involved in epigenetic histone methylation at H3K4 through the inhibition of PmisKdm5. H3K4me3 affects downstream gene expression more directly and strongly than PmisStat.

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Stat 通过抑制 KDM5 刺激萌芽褐藻成体干细胞中组蛋白 H3K4 的甲基化。

背景：鳃支上皮细胞是出芽鳞栉水母发生组蛋白 H3K4 三甲基化（H3K4me3）的主要组织之一。它在每个咽裂的底部含有增殖和未分化细胞聚集，为成体干细胞龛提供了巢穴。我们研究了成体干细胞表观遗传组蛋白甲基化的可持续机制：结果：组蛋白H3K4去甲基化酶（PmisKdm5）与转录因子、转录信号转导和激活因子（PmisStat）在体内未在同一细胞中共同表达。将 PmisStat mRNA 电穿孔到动物体内后，会抑制 PmisKdm5 的基因表达，并促进 H3K4 的三甲基化。STAT5 抑制剂阻断了 PmisStat 的核定位。无论 PmisStat mRNA 如何，它都能刺激 PmisKdm5 基因的表达。KDM5 抑制剂 CPI-455 对 H3K4me3 的刺激作用与 PmisStat mRNA 相似。PmisStat mRNA和CPI-455都能诱导PmisAp2和PmisSp8基因的表达，这两个基因最近被鉴定为萌芽/再生相关基因。当同时用 CPI-455 和 STAT5 抑制剂处理动物体组织时，CPI-455 会压制 STAT 抑制剂对 PmisAp2 和 PmisSp8 的影响：结论：PmisStat通过抑制PmisKdm5参与了H3K4的表观遗传组蛋白甲基化。H3K4me3 对下游基因表达的影响比 PmisStat 更直接、更强烈。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Developmental Dynamics 生物-发育生物学

CiteScore

5.10

自引率

8.00%

发文量

116

审稿时长

3-8 weeks

期刊介绍： Developmental Dynamics, is an official publication of the American Association for Anatomy. This peer reviewed journal provides an international forum for publishing novel discoveries, using any model system, that advances our understanding of development, morphology, form and function, evolution, disease, stem cells, repair and regeneration.