Histone deacetylases and mechanisms of regulation of gene expression

Abstract

In recent years it has become widely recognized that histone modification plays a pivotal role in controlling gene expression and is involved in a wide spectrum of disease regulation. Histone acetylation is a major modification that affects gene transcription and is controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HATs acetylate lysines of histone proteins, resulting in the relaxation of chromatin structure, and they also facilitate gene activation. Conversely, HDACs remove acetyl groups from hyperacetylated histones and suppress general gene transcription. In addition to histones, numerous nonhistone proteins can be acetylated and deacetylated, and they also are involved in the regulation of a wide range of diseases. To date there are 18 HDACs in mammals classified into 4 classes based on homology to yeast HDACs. Accumulating evidence has revealed that HDACs play crucial roles in a variety of biological processes including inflammation, cell proliferation, apoptosis, and carcinogenesis. In this review we summarize the current state of knowledge of HDACs in carcinogenesis and describe the involvement of HDACs in cancer-associated molecular processes. It is hoped than an understanding of the role of HDACs in cancer will lead to the design of more potent and specific drugs targeting selective HDAC proteins for the treatment of the disease.

Figure 1

HDAC1 performs dual roles in the regulation of acute promyelocytic leukemia: oncosuppressive in the early stages and oncogenic in established tumor cells

Figure 2

The roles of HDACs in the regulation of cancer processing. (A) HDAC1 and HDACs regulate hematological malignancies. (B) HDAC1-3 and HDAC11 regulate prostate cancer. (C) HDAC3 and HDAC4 regulate colon cancer.