scholarly journals Chromosomal architecture and placental expression of the human growth hormone gene family are targeted by pre-pregnancy maternal obesity

2018 ◽  
Vol 315 (4) ◽  
pp. E435-E445 ◽  
Author(s):  
Yan Jin ◽  
Hana Vakili ◽  
Song Yan Liu ◽  
Savas Menticoglou ◽  
Margaret E. Bock ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Rna Polymerase Ii ◽  
Maternal Obesity ◽  
Prolactin Receptor ◽  
Chromosome 17 ◽  
Growth Hormone Gene ◽  
Gene Promoters ◽  
Obese Women ◽  
Chromosome Conformation ◽  
Chromosomal Architecture

The human (h) placental lactogenic hormone chorionic somatomammotropin (CS) is highly produced during pregnancy and acts as a metabolic adaptor in response to maternal insulin resistance. Maternal obesity can exacerbate this “resistance”, and a >75% decrease in CS RNA levels was observed in term placentas from obese vs. lean women. The genes coding for hCS ( hCS-A and hCS-B) and placental growth hormone ( hGH-V) as well as the hCS-L pseudogene and pituitary growth hormone (GH) gene ( hGH-N) are located at a single locus on chromosome 17. Three remote hypersensitive sites (HS III–V) located >28 kb upstream of hGH-N as well as local hCS gene promoter and enhancer regions are implicated in hCS gene expression. A placenta-specific chromosomal architecture, including interaction between HS III–V and hCS but not hGH gene promoters, was detected in placentas from lean women (BMI <25 kg/m2) by using the chromosome conformation capture assay. This architecture was disrupted by pre-pregnancy maternal obesity (BMI >35 kg/m2), resulting in a predominant interaction between HS III and the hGH-N promoter, which was also observed in nonplacental tissues. This was accompanied by a decrease in hCS levels, which was consistent with reduced RNA polymerase II and CCAAT/enhancer-binding protein-β association with individual hCS promoter and enhancer sequences, respectively. Thus, pre-pregnancy maternal obesity disrupts the placental hGH/CS gene locus chromosomal architecture. However, based on data from obese women who develop GDM, insulin treatment partially recapitulates the chromosomal architecture seen in lean women and positively affects hCS production, presumably facilitating prolactin receptor-related signaling by hCS.

Discordant immune and growth response to pituitary and biosynthetic growth hormone in siblings with isolated growth hormone deficiency type IA

1989 ◽  
Vol 121 (5) ◽  
pp. 609-614 ◽  
Author(s):  
Berthold P. Hauffa ◽  
Ruth Illig ◽  
Toni Torresani ◽  
Herbert Stolecke ◽  
John A. Phillips
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Growth Response ◽  
Chromosome 17 ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Growth Hormone Gene ◽  
Isolated Growth Hormone Deficiency ◽  
Type Ia ◽  
Deficiency Type

Abstract. Two brothers with familial isolated growth hormone deficiency type IA homozygous for the same 6.7 kb deletion on chromosome 17 including the growth hormone gene were intermittently treated with various forms of hGH for more than 7 years. While the elder brother (Patient 1) showed a good growth response to pituitary hGH, the younger one (Patient 2) developed high titre growth blocking hGH antibodies early in the course of treatment and grew only 2.2–3.9 cm/year on a hGH dose of 12–26 IU/m2 per week. When the younger brother was changed to a higher dose (33 IU/m2 per week) of biosynthetic methionyl hGH he had striking catch-up growth and he has subsequently maintained a height velocity of 10.0 cm/year for the last 2 years. During this time his antibody titres have decreased over 1000-fold. These findings demonstrate that therapy with biosynthetic methionyl hGH may provide an effective form of treatment for subjects with isolated growth hormone deficiency type IA who do not grow in response to native hGH, and imply that biosynthetic methionyl hGH may be less antigenic than pituitary derived hGH.

A member of the nuclear factor-1 family is involved in the pituitary repression of the human placental growth hormone genes

2001 ◽  
Vol 354 (2) ◽  
pp. 387-395 ◽  
Author(s):  
Lisa Daly NORQUAY ◽  
Yan JIN ◽  
Rama Mohan SURABHI ◽  
R. Daniel GIETZ ◽  
Naoko TANESE ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Protein Interactions ◽  
Dna Sequences ◽  
Human Growth ◽  
Chromosome 17 ◽  
Gene Promoters ◽  
Nuclear Factor ◽  
Sequence Elements ◽  
Placental Growth Hormone ◽  
Nuclear Factor 1

The human growth hormone (GH) gene family consists of five tandemly arranged and highly related genes, including the chorionic somatomammotropins (CSs), at a single locus on chromosome 17. Despite striking homologies in promoter and flanking DNA sequences, the genes within this locus have different tissue-specific patterns of expression: GH-N is expressed almost exclusively in the somatotrophs of the anterior pituitary; the remaining genes, including CS-A, are expressed in placental syncytiotrophoblast. Previously we proposed that active repression of the placental gene promoters in pituitary GC cells is mediated by upstream ‘P’ sequences and, specifically, a 263bp region containing two ‘P’ sequence elements (PSE-A and PSE-B) and corresponding factors (PSF-A and PSF-B). We have now examined the possibility that PSF-A and PSF-B are members of the nuclear factor (NF)-1 family. Transcripts of NF-1A, NF-1C and NF-1X, but not of NF-1B, were readily detected in GC cells. High-affinity binding of NF-1 to PSE-B, but not to PSE-A, was confirmed by competition of DNA–protein interactions by using NF-1 DNA elements and antibodies. Functionally, a NF-1 element was able to substitute for PSE-B as a promoter-specific repressor in GC cells after gene transfer. However, there was a difference in the magnitude of repression exerted by the NF-1 and PSF-B elements on the CS-A promoter and, with the use of mutations, this difference was shown to be consistent with variations in NF-1-binding sequences. These results indicate that PSF-B, but not PSF-A, is a member of the NF-1 family, which participates in the PSF complex and in the repression of the CS-A promoter in pituitary GC cells.

scholarly journals Oscillating and stable genome topologies underlie hepatic physiological rhythms during the circadian cycle

2020 ◽  
Author(s):  
Jérôme Mermet ◽  
Jake Yeung ◽  
Félix Naef
Keyword(s):  
Rna Polymerase Ii ◽  
Clock Genes ◽  
Gene Promoter ◽  
Chromatin Interaction ◽  
Gene Promoters ◽  
Chromatin Modifications ◽  
Chromosome Conformation ◽  
Time Resolved ◽  
Liver Physiology ◽  
Stable Genome

AbstractThe circadian clock drives extensive temporal gene expression programs controlling daily changes in behavior and physiology. In mouse liver, transcription factors dynamics, chromatin modifications, and RNA Polymerase II (PolII) activity oscillate throughout the 24-hour (24h) day, regulating the rhythmic synthesis of thousands of transcripts. Also, 24h rhythms in gene promoter-enhancer chromatin looping accompany rhythmic mRNA synthesis. However, how chromatin organization impinges on temporal transcription and liver physiology remains unclear. Here, we applied time-resolved chromosome conformation capture (4C-seq) in livers of WT and arrhythmic Bmal1 knockout mice. In WT, we observed 24h oscillations in promoter-enhancer contact at multiple loci including the core-clock genes Period1, Period2 and Bmal1. In addition, we detected rhythmic PolII activity, chromatin modifications and transcription involving stable chromatin loops at gene promoters representing key liver function such as glucose and lipid metabolism and detoxification. Intriguingly, these contacts persisted in clock-impaired mice in which both PolII activity and chromatin marks no longer oscillated. Finally, we observed chromatin interaction hubs connecting neighbouring genes showing coherent transcription regulation across genotypes. Thus, both clock-controlled and clock-independent chromatin topology underlie rhythmic regulation of liver physiology.

The Turkey Transcription Factor Pit-1/GHF-1 Can Activate the Turkey Prolactin and Growth Hormone Gene Promoters in Vitro but Is Not Detectable in Lactotrophs in Vivo

2001 ◽  
Vol 123 (3) ◽  
pp. 244-253 ◽  
Author(s):  
Kristy L. Weatherly ◽  
Ramachandran Ramesh ◽  
Heather Strange ◽  
Kerry L. Waite ◽  
Brian Storrie ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Transcription Factor ◽  
Growth Hormone Gene ◽  
Gene Promoters

scholarly journals Oscillating and stable genome topologies underlie hepatic physiological rhythms during the circadian cycle

PLoS Genetics ◽  
2021 ◽  
Vol 17 (2) ◽  
pp. e1009350
Author(s):  
Jérôme Mermet ◽  
Jake Yeung ◽  
Felix Naef
Keyword(s):  
Rna Polymerase Ii ◽  
Clock Genes ◽  
Gene Promoter ◽  
Chromatin Interaction ◽  
Gene Promoters ◽  
Chromatin Modifications ◽  
Chromosome Conformation ◽  
Time Resolved ◽  
Liver Physiology ◽  
Stable Genome

The circadian clock drives extensive temporal gene expression programs controlling daily changes in behavior and physiology. In mouse liver, transcription factors dynamics, chromatin modifications, and RNA Polymerase II (PolII) activity oscillate throughout the 24-hour (24h) day, regulating the rhythmic synthesis of thousands of transcripts. Also, 24h rhythms in gene promoter-enhancer chromatin looping accompany rhythmic mRNA synthesis. However, how chromatin organization impinges on temporal transcription and liver physiology remains unclear. Here, we applied time-resolved chromosome conformation capture (4C-seq) in livers of WT and arrhythmic Bmal1 knockout mice. In WT, we observed 24h oscillations in promoter-enhancer loops at multiple loci including the core-clock genes Period1, Period2 and Bmal1. In addition, we detected rhythmic PolII activity, chromatin modifications and transcription involving stable chromatin loops at clock-output gene promoters representing key liver function such as glucose metabolism and detoxification. Intriguingly, these contacts persisted in clock-impaired mice in which both PolII activity and chromatin marks no longer oscillated. Finally, we observed chromatin interaction hubs connecting neighbouring genes showing coherent transcription regulation across genotypes. Thus, both clock-controlled and clock-independent chromatin topology underlie rhythmic regulation of liver physiology.

scholarly journals A new customised placental weight standard redefines the relationship between maternal obesity and extremes of placental size and is more closely associated with pregnancy complications than an existing population standard

2019 ◽  
Vol 11 (4) ◽  
pp. 350-359
Author(s):  
Jacqueline M. Wallace ◽  
Joeleita P. Agard ◽  
Graham W. Horgan
Keyword(s):  
Pregnancy Complications ◽  
Maternal Obesity ◽  
Population Based ◽  
Multiple Regression Model ◽  
Placental Weight ◽  
Morbidly Obese ◽  
Obese Women ◽  
Entire Cohort ◽  
Multiparous Women ◽  
The Difference

AbstractPlacental weight is a valuable indicator of its function, predicting both pregnancy outcome and lifelong health. Population-based centile charts of weight-for-gestational-age and parity are useful for identifying extremes of placental weight but fail to consider maternal size. To address this deficit, a multiple regression model was fitted to derive coefficients for predicting normal placental weight using records from healthy pregnancies of nulliparous/multiparous women of differing height and weight (n = 107,170 deliveries, 37–43 weeks gestation). The difference between actual and predicted placental weight generated a z-score/individual centile for the entire cohort including women with pregnancy complications (n = 121,591). The association between maternal BMI and placental weight extremes defined by the new customised versus population-based standard was investigated by logistic regression, as was the association between low placental weight and pregnancy complications. Underweight women had a greater risk of low placental weight [<10thcentile, OR 1.84 (95% CI 1.66, 2.05)] and obese women had a greater risk of high placental weight [>90th centile, OR 1.98 (95% CI 1.88, 2.10)] using a population standard. After customisation, the risk of high placental weight in obese/morbidly obese women was attenuated [OR 1.17 (95% CI 1.09, 1.25)]/no longer significant, while their risk of low placental weight was 59%–129% higher (P < 0.001). The customised placental weight standard was more closely associated with stillbirth, hypertensive disease, placental abruption and neonatal death than the population standard. Our customised placental weight standard reveals higher risk of relative placental growth restriction leading to lower than expected birthweights in obese women, and a stronger association between low placental weight and pregnancy complications generally. Further, it provides an alternative tool for defining placental weight extremes with implications for the placental programming of chronic disease.

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