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Histone Acetylases (HATs) and Histone Deacetylases (HDACs)

The control of gene expression is dependent on many things. Transcription factors binding to specific DNA regions triggers the initiation of transcription and the production of mRNA molecules. An additional level of control is the actual structure of DNA to which the transcription factors bind. Our chromosomes are composed of large amounts of DNA that is bound to proteins called histones. The DNA wraps around the histone proteins and forms bead-like structures called nucleosomes, shown below.

The ability of a particular transcription factor to bind to its target gene is, in part, dependent on modifications that are made to the histone proteins. Enzymes called histone acetyl transferases (HATs) alter the chromatin (DNA:protein) structure by adding short carbon chains to some histone proteins. This alteration changes the structure of the DNA:histone interaction loosening up the 'bead', allowing transcription factors to bind. A separate group of enzymes, histone deacetlyases (HDACs), is responsible for removing the acetyl groups from the histones, shutting down transcription.

Abnormal activity of HDACs has been observed in several different types of cancer, such as acute promyelocytic leukemia, acute myelogenous leukemia, non-Hodgkin lymphoma, and some types of colorectal and gastric carcinomas. When these enzymes act incorrectly, they can prevent the transcription of key genes. This process appears to be an important step in the tumorigenic process in some forms of cancer.

A closer look at chromatin structure and gene expression