Growth hormone response element gene transcriptions

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Associate Editor(s)-in-Chief: Henry A. Hoff

Human genes

Gene ID: 2688 is GH1 growth hormone 1: "The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. This particular family member is expressed in the pituitary but not in placental tissue as is the case for the other four genes in the growth hormone locus. Mutations in or deletions of the gene lead to growth hormone deficiency and short stature."[1]

Consensus sequences

"Computer analysis of the nt −653 to nt −483 region identified two sites that resemble the [γ-interferon activated sequence] GAS consensus sequence, TTNCNNNAA (19). Similar GAS-like sites have been shown to mediate the effects of various cytokines, including [growth hormone] GH, on the transcription of other genes (19, 20). The first site, TTCCTAGAA (ALS-GAS1), is located between nt −633 and nt −625; the second site, TTAGACAAA (ALS-GAS2), is located between nt −553 and nt −545."[2]

"To ascertain whether one or both of these two ALS-GAS sites were functionally important for GH stimulation of ALS promoter activity, plasmids containing block mutations of either ALS-GAS1 [...] or ALS-GAS2 [...] were prepared in the context of the luciferase construct retaining full responsiveness to GH [...], and transfected into H4-II-E cells [...]. Mutation of the ALS-GAS1 element abolished the ability of the promoter to respond to GH [...]; mutation of the ALS-GAS2 element was without effect. Thus, an intact ALS-GAS1 element is necessary for GH stimulation of ALS promoter activity."[2]

Comparison of GAS-Like Elements Shown to Mediate the Effect of GH on Chromosomal Genes:[2]
Name of element Sequence Preferred STAT Gene and reference
Spi-GLE1 TTC TGA GAA STAT5 Rat Spi 2.1 (27)
INS-GLE TTC TGG GAA STAT5 Rat insulin (29)
CYPGHRE TTC CTG GAA STAT5 Hamster CYP3A10/6β (30)
ALS-GAS1 TTC CTA GAA STAT5 Mouse ALS (this study)
SIE TTC CCG TAA STAT1 and 3 Rat c-fos (22,57–59)
m67 TTC CCG TCA STAT1 and 3 Optimized c-fos SIE (22)

See also

References

  1. RefSeq (July 2008). "GH1 growth hormone 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 9 September 2020.
  2. 2.0 2.1 2.2 Guck T. Ooi, Kelley R. Hurst, Matthew N. Poy, Matthew M. Rechler, Yves R. Boisclair (1 May 1998). "Binding of STAT5a and STAT5b to a Single Element Resembling a γ-Interferon-Activated Sequence Mediates the Growth Hormone Induction of the Mouse Acid-Labile Subunit Promoter in Liver Cells". Molecular Endocrinology. 12 (5): 675–687. doi:10.1210/mend.12.5.0115. PMID 9605930. Retrieved 9 September 2020.

External links