Activation of the human GH gene cluster: roles for targeted chromatin modification

The cluster of genes encoding the human growth hormone (GH) contains an array of five highly related genes. From 5' to 3' these are: GHN, CSL (encoding chorionic somatomammotropin-like gene), CSA, GHV (encoding GH-variant gene) and CSB. These five genes are expressed in mutually exclusive tissue distributions, GHN in pituitary somatotropes and the remaining four genes in placental villous syncytiotrophoblasts. The onset of GH expression during development is dependent upon epigenetic modifications at the GH locus under the control of its distal locus control region (LCR). A clear understanding of these normal epigenetic controls on the expression of GH could lead to new insights into the development and treatment of isolated GH deficiency in children. This review focuses on the role of the LCR in histone hyperacetylation at the GH locus and subsequent effects on the tissue-specific activation of these genes.