Histone Acetyltransferases and Stem Cell Identity.

Abstract

Simple SummaryGene 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.