肠道微生物群-宿主互作中的染色质动态和组蛋白修饰。

Chromatin dynamics and histone modifications in intestinal microbiota-host crosstalk.

机构信息

Babraham Institute, Babraham, Cambridge, CB22 3AT, UK.

Babraham Institute, Babraham, Cambridge, CB22 3AT, UK; School of Life Sciences, University of Essex, Colchester, CO4 3SQ, UK.

出版信息

Mol Metab. 2020 Aug;38:100925. doi: 10.1016/j.molmet.2019.12.005. Epub 2019 Dec 27.

Abstract

BACKGROUND

The microbiota in the human gut are an important component of normal physiology that has co-evolved from the earliest multicellular organisms. Therefore, it is unsurprising that there is intimate crosstalk between the microbial world in the gut and the host. Genome regulation through microbiota-host interactions not only affects the host's immunity, but also metabolic health and resilience against cancer. Chromatin dynamics of the host epithelium involving histone modifications and other facets of the epigenetic machinery play an important role in this process.

SCOPE OF REVIEW

This review discusses recent findings relevant to how chromatin dynamics shape the crosstalk between the microbiota and its host, with a special focus on the role of histone modifications.

MAJOR CONCLUSIONS

Host-microbiome interactions are important evolutionary drivers and are thus expected to be hardwired into and mould the epigenetic machinery in multicellular organisms. Microbial-derived short-chain fatty acids (SCFA) are dominant determinants of microbiome-host interactions, and the inhibition of histone deacetylases (HDACs) by SCFA is a key mechanism in this process. The discovery of alternative histone acylations, such as crotonylation, in addition to the canonical histone acetylation reveals a new layer of complexity in this crosstalk.

摘要

背景

人类肠道中的微生物群是正常生理的一个重要组成部分,它是从最早的多细胞生物中共同进化而来的。因此,肠道中的微生物世界与宿主之间存在密切的相互作用并不奇怪。通过微生物-宿主相互作用进行的基因组调控不仅影响宿主的免疫,还影响代谢健康和对癌症的抵抗力。涉及组蛋白修饰和表观遗传机制其他方面的宿主上皮细胞染色质动力学在这个过程中起着重要作用。

综述范围

这篇综述讨论了与染色质动力学如何塑造微生物群与其宿主之间的相互作用相关的最新发现,特别关注组蛋白修饰的作用。

主要结论

宿主-微生物群相互作用是重要的进化驱动因素,因此预计会被内置到多细胞生物的表观遗传机制中,并对其进行塑造。微生物衍生的短链脂肪酸(SCFA)是微生物群-宿主相互作用的主要决定因素,SCFA 抑制组蛋白去乙酰化酶(HDAC)是该过程的关键机制。除了经典的组蛋白乙酰化之外,还发现了其他组蛋白酰化,如丙二酰化,这揭示了这种相互作用的新复杂性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b81/7300386/1a75cf581a81/gr1.jpg

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