[PDF][PDF] Locus control region transcription plays an active role in long-range gene activation

Y Ho, F Elefant, SA Liebhaber, NE Cooke - Molecular cell, 2006 - cell.com
Y Ho, F Elefant, SA Liebhaber, NE Cooke
Molecular cell, 2006cell.com
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 …
Summary
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 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.
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