The human growth hormone locus: Nucleotide sequence, biology, and evolution

Chen, Ellson Y.; Liao, Yu−Cheng; Smith, Douglas H.; Barrera-Saldaña, Hugo A.; Gelinas, Richard; Seeburg, Peter H.

doi:10.1016/0888-7543(89)90271-1

Cited by 449 publications

(312 citation statements)

References 25 publications

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“…However, the degree to which these models accurately reflect the full array of locus control region (LCR) functions remains to be determined and might vary among loci. The human growth hormone (hGH) cluster contains one pituitary-specific hGH-N gene and four placenta-specific paralogues (Fig 1A;Chen et al, 1989). These five genes are activated by a set of LCR determinants located 15-32 kb upstream of the cluster ( Jones et al, 1995;Su et al, 2000;Ho et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

The juxtaposition of a promoter with a locus control region transcriptional domain activates gene expression

Tadevosyan

Liebhaber

et al. 2008

EMBO Reports

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Nonlinear chromatin configurations can juxtapose widely separated elements within a genomic locus; however, it remains unclear how these structures are established and contribute to transcriptional control. A 5 0 -remote locus control region (LCR) regulates the human growth hormone (hGH-N) gene. HSI, a pituitary-specific component of the hGH LCR, establishes a domain of polymerase II (PolII) transcription 5 0 to hGH-N. Repression of this transcriptional domain by HSI deletion or PolII blockade decreases hGH-N expression. Here, we show that hGH-N activation is accompanied by positioning of the hGH-N promoter to this LCR transcriptional domain. Selectively blocking LCR transcription inhibits the formation of this active 'looped' conformation. Thus, HSI is crucial for establishing a domain of noncoding PolII transcription, and this domain is intimately linked with chromatin organization of the active hGH-N locus. This integration of LCR transcription with chromatin reconfiguration constitutes a robust pathway for long-range gene activation.

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Section: Introductionmentioning

confidence: 99%

The juxtaposition of a promoter with a locus control region transcriptional domain activates gene expression

Tadevosyan

Liebhaber

et al. 2008

EMBO Reports

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“…Characterization of Human LIFR Placenta-specific Enhancerenhancer was active in choriocarcinoma JEG-3 and JAR cells, and inactive in cell lines derived from nonplacental tissues such as liver, bone marrow, thyroid, breast, and lung (25). At that time, we did not specifically test pituitary cell lines, but placental and pituitary cells share considerable similarities for transcriptional regulation of several genes, including growth hormone, glycoprotein hormone ␣ subunit, chorionic somatomammotropin B (CS-B, or placental lactogen, PL) (27)(28)(29). We therefore chose several available pituitary cell lines, namely ACTH-producing AtT20 and growth hormone secreting GH4 and GC cell lines to further test the specificity of the cloned LIFR gene enhancer and two LIFR promoters.…”

Section: Methodsmentioning

confidence: 99%

Functional Map of a Placenta-specific Enhancer of the Human Leukemia Inhibitory Factor Receptor Gene

Wang

Melmed

1998

Journal of Biological Chemistry

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We recently reported a placenta-specific enhancer in the human leukemia inhibitory factor receptor (LIFR) gene and now show detailed characterization of the 226-base pair enhancer (؊4625/؊4400 nucleotides). Four of twenty-two mutants in linker analysis showed reduced promoter activities to 45, 30, 10, and 10%, respectively. Specific binding of region A (؊4617/؊4602) with nuclear extract was competed by a known Oct-1 oligo and supershifted by Oct-1 antibody. Specific binding of region B (؊4549/؊4535) was competed by a GATA oligo, but could not be supershifted by four GATA antibodies. Nevertheless, mutagenesis showed that critical bases in region B were identical to the GATA core motif, indicating that region B may bind to a novel GATA family transcription factor. The other two adjacent regions designated as region C (؊4464/؊4445) showed no known consensus binding sites, and their specific placental JEG-3 nuclear extract binding was not evident in nonplacental nuclear extracts and was not competed by a trophoblast specific element (TSE), indicating that region C is a novel placenta-specific element (PSE, CATTTCCTGAACTAGTT-TTT). Footprinting localized the binding boundary of PSE-binding protein (PSEB), and three Gs were found to be important for specific PSE binding. UV cross-linking showed that PSEB had a molecular mass of ϳ160 kDa, substituting the PSE with two previously reported placenta elements TSE or chorionic somatomammotropin enhancer factor 1 (CSEF-1) motifs resulted in markedly different promoter activities, indicating that PSEB is indeed different from TSE binding protein or CSEF-1. These results are the first demonstration that a novel PSE is the major element for placenta-specific enhancer activity in human LIFR gene.

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“…Anthropoid primates possess a cluster of GH-related genes [31,32]. All genes of a cluster are, strictly speaking, orthologs of the single GH gene of other mammals.…”

Section: Primatesmentioning

confidence: 99%

“…But, one gene is usually singled out as the 'true' GH, based on its expression in pituitary somatotrophs. The additional genes of apes and Old World monkeys are expressed in the placenta [32,33] but this has not been determined in New World monkeys. All GHlike proteins of New World monkeys are more similar to each other than to any GH-like protein of apes or Old World monkeys, suggesting independent duplications of GH in the two lineages [34].…”

Section: Primatesmentioning

confidence: 99%

“…GH1 encodes human growth hormone (hGH), GH2 encodes human placental growth hormone (hPGH), and CSH1 and CSH2 encode human placental lactogen (hPL) [32]. These hormones have different relative affinities for GHRs and PRLRs: hGH binds to both GHRs and PRLRs; hPL has high affinity for PRLRs but very weak affinity for GHRs [35]; and hPGH has high affinity for GHRs but negligible affinity for human PRLRs [36].…”

Section: Primatesmentioning

confidence: 99%

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