Previous work in the laboratories of Cooke and Liebhaber found that the hGH gene is controlled by a non-coding DNA region, or locus control region. Remarkably, this region is located more than 14,000 base pairs away from the hGH gene. At the genomic level, a 14,000 base-pair separation is equal to the size of 10 growth hormone genes lined end to end. "The effects of the locus control region on human growth hormone expression is as if you turn a key in the lock of a house at one end of your street and find that this action opens the lock and door of a house a block away," notes Liebhaber.
By carefully analyzing the 14,000 base pairs separating the hGH gene and its locus control region, co-authors Yugong Ho, PhD, an Instructor of Genetics at Penn and a Cooke/Liebhaber lab member, and Felice Elefant, PhD, Assistant Professor at Drexel University and former member of the Cooke/Liebhaber lab, found that the locus control region was copied into RNA, and discovered a gene called CD79b within this region. Remarkably this CD79b gene was also copied into RNA in the pituitary. While the CD79b gene normally codes for a protein in blood lymphocytes, researchers discovered that CD79b appears to play a very different role in the pituitary gland. Here, CD79b was actively transcribed into mRNA, but this mRNA failed to translate into a functional protein. Instead, the non-coding RNA was suspected to play a role in hGH gene regulation.
In order to determine whether the CD79b RNA in the pituitary gland served a function, Ho inserted a segment of human DNA that included hGH, the hGH locus control region, and CD79b into a group of mice. As a result, the transgenic mice expressed high levels of human growth hormone in the pituitary as well as mouse growth hormone. To test whether the transcription of the locus control region and CD79b played a significant role in hGH expressi
Contact: Karen Kreeger
University of Pennsylvania School of Medicine