Enhancer-Blocking Activity Is Associated with Hypersensitive Site V Sequences in the Human Growth Hormone Locus Control Region

2011 ◽  
Vol 30 (12) ◽  
pp. 995-1005 ◽  
Author(s):  
Yan Jin ◽  
Kevin Oomah ◽  
Peter A. Cattini
Keyword(s):  
Growth Hormone ◽  
Control Region ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Locus Control Region ◽  
Hypersensitive Site ◽  
Blocking Activity ◽  
Enhancer Blocking

POU1F1-Mediated Activation of hGH-N by Deoxyribonuclease I Hypersensitive Site II of the Human Growth Hormone Locus Control Region

2012 ◽  
Vol 415 (1) ◽  
pp. 29-45 ◽  
Author(s):  
Tamra L. Hunsaker ◽  
Holly S. Jefferson ◽  
J. Kaitlin Morrison ◽  
Andrew J. Franklin ◽  
Brian M. Shewchuk
Keyword(s):  
Growth Hormone ◽  
Control Region ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Locus Control Region ◽  
Hypersensitive Site ◽  
Deoxyribonuclease I

scholarly journals The human growth hormone gene is regulated by a multicomponent locus control region.

1995 ◽  
Vol 15 (12) ◽  
pp. 7010-7021 ◽  
Author(s):  
B K Jones ◽  
B R Monks ◽  
S A Liebhaber ◽  
N E Cooke
Keyword(s):  
Growth Hormone ◽  
Gene Cluster ◽  
Control Region ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Locus Control Region ◽  
Dnase I ◽  
N Gene ◽  
Regulatory Sequences ◽  
Growth Hormone Gene

The five-member human growth hormone (hGH)/chorionic somatomammotropin (hCS) gene cluster encodes the pituitary-specific hGH-N gene and four highly related genes (hGH-V, hCS-A, hCS-B, and hCS-L) that are expressed only in the placenta. When the hGH-N or hCS-A gene, together with all previously identified cis-acting regulatory sequences, was integrated into the mouse genome, it was expressed only sporadically and at low levels in the transgenic target organs. DNase I mapping of chromatin from expressing and nonexpressing cell types was used to identify a pituitary-specific set of DNase I-hypersensitive sites (HS) and a set of HS common to both the pituitary and placenta, centered approximately 15 and 30 kb 5' of hGH-N, respectively. When contained on a cosmid insert in their native genomic configuration, these HS consistently directed high-level, pituitary-specific expression of hGH-N in transgenic mice and appeared to define a locus control region required for hGH-N expression. Individually, each set of HS was able to mediate position-independent hGH-N expression in the pituitary but demonstrated loss of physiologic control and loss of tissue specificity. The gene-proximal set of HS contained a potent enhancer activity in the pituitary, while the more distal set appeared to function primarily to establish site-of-integration independence. These data indicate that synergistic interactions among multiple elements are required to restrict hGH-N transcription to the pituitary and generate appropriate levels of expression. In addition, these results suggest a role for both shared and unique regulatory sequences in locus control region-mediated expression of the hGH/hCS gene cluster in the pituitary and possibly the placenta.

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