Locus control region transcription plays an active role in long-range gene activation.

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 HSI [corrected] dependent and terminates 3' 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.