Bystander gene activation by a locus control region

Locus control regions (LCRs) are regulatory elements that can activate high levels of gene transcription from remote locations relative to target genes. Transcription of the human growth hormone (hGH) gene cluster depends on epigenetic regulation by an hGH LCR located 16-32kb upstream of the cluster. The hGH LCR may establish an extensive activated chromatin domain that encompasses target hGH gene promoters. The immunoglobulin associated beta gene (hIgβ), which plays a specific role in B-cell differentiation, is situated between the hGH LCR and the hGH gene cluster on chromosome 17. Gene expression experiments predictably found hIgβ transcription in the spleen, but unexpectedly found strong hIgβ transcription in human pituitary tissues. A lack of function ascribed to hIgβ in the pituitary combined with the expectation that insulator/boundary regulatory elements would shield hIgβ from epigenetic alterations associated with the hGH LCR hyper-acetylated chromatin domain in which it is located, suggested an unlikeliness of robust pituitary transcription.

The fortuitous positioning of hIgβ as a ‘bystander’ within the activated domain is a likely pituitary-specific explanation for hIgβ transcription in the pituitary. This unexpected finding impacts on current concepts of tissue specificity and suggests that simple linear insulator/boundary models of gene insulation may be insufficient.

Shaun Mason

[Journal article reference: Cajiao, I., Zhang, A., Jae Yoo, E., Cooke, N.E., & Liebhaber, S.A. (2004). Bystander gene activation by a locus control region, EMBO, 23(19), 3854-3863.]