Energy homeostasis targets chromosomal reconfiguration of the human GH1 locus

Vakili, Hana; Jin, Yan; Cattini, Peter A.

doi:10.1172/jci77126

Cited by 12 publications

(14 citation statements)

References 65 publications

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“…To our knowledge, this is the first study to use a murine system to observe the effect of SD on hGH synthesis, as studies on hGH-N RNA levels in the pituitary are not possible in living humans. As expected, the consumption of a HFD for three to four days did not cause significant weight gain (12,13), but there was evidence of stress due to acute SD that was independent of diet.…”

Section: Discussionsupporting

confidence: 73%

Sleep deprivation and diet affect human GH gene expression in transgenic mice in vivo

Jarmasz

Jin

Vakili

et al. 2020

Endocrine Connections

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Human (h) growth hormone (GH) production studies are largely limited to effects on secretion. How pituitary hGH gene (hGH-N/GH1) expression is regulated is important in our understanding of the role hGH plays in physiology and disease. Here we assess for the first time the effect of sleep deprivation (SD) and high-fat diet (HFD) on hGH-N expression in vivo using partially humanized 171hGH/CS transgenic (TG) mice, and attempted to elucidate a role for DNA methylation. Activation of hGH-N expression requires interactions between promoter and upstream locus control region (LCR) sequences including pituitary-specific hypersensitive site (HS) I/II. Both SD and diet affect hGH secretion, but the effect of SD on hGH-N expression is unknown. Mice fed a HFD or regular chow diet for three days underwent SD (or no SD) for 6 hours at zeitgeber time (ZT) 3. Serum and pituitaries were assessed over 24 hours at 6-hour intervals beginning at ZT 14. SD and HFD caused significant changes in serum corticosterone and insulin, as well as hGH and circadian clock-related gene RNA levels. No clear association between DNA methylation and the negative effects of SD or diet on hGH RNA levels was observed. However, a correlation with increased methylation at a CpG (cytosine paired with a guanine) in a putative E-box within the hGH LCR HS II was suggested in situ. Methylation at this site also increased BMAL1/CLOCK-related nuclear protein binding in vitro. These observations support an effect of SD on hGH synthesis at the level of gene expression.

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Section: Discussionsupporting

confidence: 73%

Sleep deprivation and diet affect human GH gene expression in transgenic mice in vivo

Jarmasz

Jin

Vakili

et al. 2020

Endocrine Connections

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“…In the thyroid, 133 autosomal genes were sex-biased, 75% of which were expressed more highly in males. Genes that encode for growth factors and signaling molecules were highly expressed in the thyroid of males, such as CCL28 , a growth factor in hematopoietic stem cells (Karlsson et al, 2013 ), CMTM4 , a chemokine that regulates the cell cycle (Plate et al, 2010 ), and GH1 , a gene that encodes for growth hormone (Vakili et al, 2014 ). These findings suggest a functional role for the thyroid in influencing sexually dimorphic traits such as metabolism, as well as sex differences in thyroid hormone secretion (Ehrenkranz et al, 2015 ).…”

Section: Resultsmentioning

confidence: 99%

Large Scale Gene Expression Meta-Analysis Reveals Tissue-Specific, Sex-Biased Gene Expression in Humans

et al. 2016

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The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analyzed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes), followed by the heart (375 genes), kidney (224 genes), colon (218 genes), and thyroid (163 genes). More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs, and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases.

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“…Disruption of the Pit-1 complex and chromosomal loop, including through a high fat vs regular chow diet in partially humanised 171 hGH/CS transgenic mice, has a negative effect on hGH-N/GH1 expression. 67,70,71 To date, no placenta-specific factor, equivalent to pituitary-specific Pit-1 and capable of binding hPL LCR and gene promoter sequences, has been identified. However, the zinc finger DNA-binding transcription factor paternally-expressed gene 3 (PEG3/PW1), the imprinted gene product of the paternal allele, has emerged as a potential candidate.…”

Section: Peg3/pw1: a P Oss Ib Le C And Idate For Pl Acental Controlmentioning

confidence: 99%

Obesity and regulation of human placental lactogen production in pregnancy

Cattini

Jin

Jarmasz

et al. 2020

J Neuroendocrinology

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The four genes coding for placental members of the human (h) growth hormone (GH) family include two that code independently for placental lactogen (PL), also known as chorionic somatomammotrophin hormone, one that codes for placental growth hormone (PGH) and a pseudogene for which RNA but no protein product is reported. These genes are expressed preferentially in the villus syncytiotrophoblast of the placenta in pregnancy. In higher primates, the placental members, including hPL and PGH, are the result of multiple duplication events of the GH gene.

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Energy homeostasis targets chromosomal reconfiguration of the human GH1 locus

Cited by 12 publications

References 65 publications

Sleep deprivation and diet affect human GH gene expression in transgenic mice in vivo

Sleep deprivation and diet affect human GH gene expression in transgenic mice in vivo

Large Scale Gene Expression Meta-Analysis Reveals Tissue-Specific, Sex-Biased Gene Expression in Humans

Obesity and regulation of human placental lactogen production in pregnancy

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