Histone Acetyltransferases and Stem Cell Identity.
Histone Acetyltransferases and Stem Cell Identity.
复制标题
DOI：
10.3390/cancers13102407
复制
发表时间：
2021-05-17
期刊：
影响因子：
5.2
通讯作者：
Riabowol K
中科院分区：
文献类型：
--
作者：
He R;Dantas A;Riabowol K
基因调控是使我们能够从单个细胞发育成包含许多器官和组织的完全形成的成人身体的主要机制，>200种细胞类型和总共约50万亿个细胞。我们的细胞将基因“打开和关闭”的方式之一是通过添加或去除乙酰基部分（CH 3CO）到称为组蛋白的蛋白质中。我们的DNA被包裹在8个组蛋白的组周围形成核小体，从而稳定和压缩。在组蛋白上添加乙酰基可以使包裹变得松散，使DNA更容易转录，从而“打开”感兴趣的基因。这个过程由称为组蛋白乙酰转移酶（HAT，也称为赖氨酸乙酰转移酶）和组蛋白脱乙酰酶（HDAC或赖氨酸脱乙酰酶）的酶协调。这些酶活性的精确协调对于使我们的干细胞群能够自我补充或沿着沿着不同的途径分化是必不可少的。这些酶中的许多已被描述为造血干细胞、脑干细胞和间充质干细胞的关键调节剂。本文综述了HAT和HDAC如何调节干细胞过程，以及目前已知的组蛋白乙酰化在干细胞生物学中的作用。组蛋白乙酰化是转录调控中的一个重要表观遗传修饰。向组蛋白尾部添加乙酰基通常减少核小体中的组蛋白-DNA相互作用，导致转录因子和核心转录机制结合其靶序列的可及性增加。大约有30种组蛋白乙酰转移酶及其相应的复合物，每一种都会影响一个基因子集的表达。由于细胞身份是由基因表达谱决定的，因此负责诱导这些基因表达的HAT在决定细胞命运中起关键作用并不奇怪。在这里，我们探讨了HAT在各种干细胞类型的维持和分化中的作用。几种HAT复合物已被表征为在激活允许干细胞自我更新的基因中发挥重要作用。其活性的敲低或丧失导致表达和/或分化减少，而特定的HAT驱动朝向特定细胞命运的分化。在这项研究中，我们审查的HAT复合物的功能，多能干细胞，造血干细胞，肌肉卫星细胞，间充质干细胞，神经干细胞和癌症干细胞的活性。
Gene regulation is the major mechanism that allows us to develop from a single cell to a fully formed adult body containing numerous organs and tissues, >200 cell types and a total of about 50 trillion cells. One of the ways our cells turn genes “on and off” is through the addition or removal of acetyl moieties (CH3CO) to proteins called histones. Our DNA is stabilized and compacted by being wrapped around groups of 8 histones to form nucleosomes. The addition of acetyl groups to histones loosens that wrapping, allowing the DNA to be more accessible for transcription, “turning on” genes of interest. This process is coordinated by enzymes called histone acetyltransferases (HATs, also called lysine acetyltransferases) and histone deacetylases (HDACs or lysine deacetylases). The precise coordination of these enzyme activities is essential to allow our stem cell populations to replenish themselves or differentiate along different pathways. Many of these enzymes have been described as being key regulators for hematopoietic, brain, and mesenchymal stem cells. This review describes how HATs and HDACs regulate stem cell processes and what is currently known regarding the roles of acetylation of histones in stem cell biology. Acetylation of histones is a key epigenetic modification involved in transcriptional regulation. The addition of acetyl groups to histone tails generally reduces histone-DNA interactions in the nucleosome leading to increased accessibility for transcription factors and core transcriptional machinery to bind their target sequences. There are approximately 30 histone acetyltransferases and their corresponding complexes, each of which affect the expression of a subset of genes. Because cell identity is determined by gene expression profile, it is unsurprising that the HATs responsible for inducing expression of these genes play a crucial role in determining cell fate. Here, we explore the role of HATs in the maintenance and differentiation of various stem cell types. Several HAT complexes have been characterized to play an important role in activating genes that allow stem cells to self-renew. Knockdown or loss of their activity leads to reduced expression and or differentiation while particular HATs drive differentiation towards specific cell fates. In this study we review functions of the HAT complexes active in pluripotent stem cells, hematopoietic stem cells, muscle satellite cells, mesenchymal stem cells, neural stem cells, and cancer stem cells.
登录
查看更多内容
影响因子：
4
作者：
Brownell, JE;Allis, CD
通讯作者：
Allis, CD
影响因子：
4.6
作者：
Gao C;Bourke E;Scobie M;Famme MA;Koolmeister T;Helleday T;Eriksson LA;Lowndes NF;Brown JA
通讯作者：
Brown JA
影响因子：
64.8
作者：
Baell, Jonathan B.;Leaver, David J.;Thomas, Tim
通讯作者：
Thomas, Tim
影响因子：
50.3
作者：
Deguchi, K;Ayton, PM;Gilliland, DG
通讯作者：
Gilliland, DG
影响因子：
6.8
作者：
Berndsen, Christopher E.;Denu, John M.
通讯作者：
Denu, John M.