短链脂肪酸调节染色体格局和人类结肠直肠癌细胞中明显的基因表达变化
Tohfa Kabir1, Charlotte A Connamacher1, Zara Nadeem2,3
1Department of Biochemistry, Case Western Reserve University, Cleveland, OH.
bioRxiv : the preprint server for biology
|June 4, 2025
概括
短链脂肪酸 (SCFA) 改变了人体细胞中的染色质格局. 这些微生物代谢物,如丁酸盐,改变了结直肠癌中的基因调节,影响了基因程序.
科学领域:
- 微生物学 微生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 短链脂肪酸 (SCFA) 是微生物代谢物,对人类生理学至关重要.
- 通过修改染色体景观,SCFA与宿主相互作用.
- 之前的研究在小鼠中发现了SCFA衍生的基因组修饰,但它们在人类细胞中的作用仍然不清楚.
研究的目的:
- 研究微生物群依赖的基因组转化后修饰 (PTMs) 对人类细胞基因调节的影响.
- 确定SCFA如何影响人类结直肠癌中的染色质和基因表达.
主要方法:
- 在人类结肠样本中对H3K27的基因组丁化分析.
- 评估SCFA对人类结肠癌细胞系中的基化,丁基化和基化的影响.
- 用单个和组合的SCFA治疗细胞系,观察基因程序的变化.
- 调查丁酸盐的基因表达效应,独立于HDAC抑制,并依赖于p300/CBP.
主要成果:
- 在人类结肠样本中检测到H3K27上的基基激素.
- 在癌症细胞系中,SCFA水平调节了癌细胞系中的H3K9和H3K27的基因组修饰 (乙化,丁化,化),与活性基因调节元素相关.
- SCFA 治疗诱导了明显的和重叠的基因程序改变,其中丁酸盐是主要的驱动因素.
- 发现丁酸盐的基因表达效应与HDAC无关,与p300/CBP无关.
结论:
- 微生物群依赖的基因组PTM与人类细胞中基因调节的改变有关.
- 在人类结直肠癌中,SCFA是染色质景观和基因程序的关键调节者.
- 丁酸盐通过涉及p300/CBP的机制在SCFA介导的基因调节中发挥着重要作用.
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