Journal
MOLECULAR CELL
Volume 23, Issue 3, Pages 365-375Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2006.05.041
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Funding
- NCI NIH HHS [P30 CA016520] Funding Source: Medline
- NICHD NIH HHS [R01 HD25147, R01 HD025147] Funding Source: Medline
- NIDDK NIH HHS [K01 DK064011, P30 DK019525, P30 DK050306] Funding Source: Medline
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Activation of eukaryotic genes often relies on remote chromatin determinants. How these determinants function remains poorly understood. The hGH gene is activated by a 5'-remote locus control region (LCR). Pituitary-specific DNase I hypersensitive site I (HSI), the dominant hGH LCR element, is separated from the hGH-N promoter by a 14.5 kb span that encompasses the B-lymphocyte-specific CD79b gene. Here, we describe a domain of noncoding Pol II transcription in pituitary somatotropes that includes the hGH LCR and adjacent CD79b locus. This entire LCR domain of transcription is HIS dependent and terminates 31 to CD79b, leaving a gap in transcription between this domain and the target hGH-N promoter. Insertion of a Pol II terminator within the LCR blocks CD79b transcription and represses hGH-N expression. These data document an essential role for LCR transcription in long-range control, link bystander CD79b transcription to this process, and support a unique model for locus activation.
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