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Sökning: WFRF:(Ekstrom TJ)

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  • von Horn, H, et al. (författare)
  • GH is a regulator of IGF2 promoter-specific transcription in human liver
  • 2002
  • Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 172:3, s. 457-465
  • Tidskriftsartikel (refereegranskat)abstract
    • The regulation of the insulin-like growth factor-II gene (IGF2) is complex and involves the usage of four promoters resulting in different 5' untranslated regions, but with a common translated product. The IGF2 gene product is a mitogenic and survival factor that has been suggested to be important for a normal fetal development and cancer. In this paper we present evidence suggesting that the human IGF2 gene is regulated by GH, and that this regulation occurs in a promoter-specific way. Three lines of evidence support this finding. First, in vivo data from patients treated with GH (one injection or daily injections for 5 consecutive days) showed an increase in the IGF2 P2 promoter derived transcript after acute treatment, and of the P4 promoter transcript after short-term treatment while the P1 promoter derived transcript did not show any significant change. Secondly, isolated human liver cells treated with GH for 2 h displayed an upregulation of the P2 promoter derived transcript. Thirdly, employing transfection experiments in GH-receptor positive CHO cells with P2 and P4 promoter-luciferase constructs, an upregulation by GH was evident, while a P1 promoter construct was unresponsive. We suggest that GH may be a physiological regulator of IGF2 in humans.
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  • Efstathopoulos, P, et al. (författare)
  • NR3C1 hypermethylation in depressed and bullied adolescents
  • 2018
  • Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 8:1, s. 121-
  • Tidskriftsartikel (refereegranskat)abstract
    • The disruption of key epigenetic processes during critical periods of brain development can increase an individual’s vulnerability to psychopathology later in life. For instance, DNA methylation in the glucocorticoid receptor gene (NR3C1) in adulthood is known to be associated with early-life adversities and has been suggested to mediate the development of stress-related disorders. However, the association between NR3C1 methylation and the emergence of internalizing symptoms in childhood and adolescence has not been studied extensively. In the present report, we used saliva DNA from a cohort of Swedish adolescents (13–14 years old; N = 1149) to measure NR3C1 methylation in the exon 1F region. Internalizing psychopathological symptoms were assessed using the Center for Epidemiologic Studies Depression Scale for Children (CES-DC). We found that NR3C1 hypermethylation was cross-sectionally associated with high score for internalizing symptoms in the whole group as well as among the female participants. In addition, an analysis of social environmental stressors revealed that reports of bullied or lacking friends were significantly associated with NR3C1 hypermethylation. This cross-sectional association of NR3C1 exon 1F hypermethylation with internalizing psychopathology in adolescents, as well as with bullying and lack of friends are novel results in this field. Longitudinal studies are needed to address whether NR3C1 methylation mediates the link between social stressors and psychopathology in adolescence.
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  • Ekstrom, TJ (författare)
  • Epigenetic control of gene expression
  • 2009
  • Ingår i: Biochimica et biophysica acta. - : Elsevier BV. - 0006-3002 .- 0304-4165. ; 1790:9, s. 845-846
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • EKSTROM, TJ, et al. (författare)
  • PROMOTER-SPECIFIC IGF2 IMPRINTING STATUS AND ITS PLASTICITY DURING HUMAN LIVER DEVELOPMENT
  • 1995
  • Ingår i: DEVELOPMENT. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 121:2, s. 309-316
  • Tidskriftsartikel (refereegranskat)abstract
    • IGF2 has been shown to be expressed preferentially from the paternally derived allele, although the maternal allele can be found active during both prenatal and postnatal development as well as in neoplastic tumours in humans. We addressed here whether or not the biallelic expression patterns that can be seen during postnatal human liver development reflected a coordinated change in the activities of the four promoters of human IGF2. We show here that the P2, P3 and P4 promoters, but not the P1 promoter, display monoallelic activity in embryonic, neonatal and younger infant liver specimens. The P2, P3 and P4 promoters can, however, be found active either monoallelically or biallelically or even monoallelically on opposite parental alleles in older infant and adult liver specimens. In contrast, H19, which is closely linked to IGF2, is monoallelically expressed in all postnatal liver samples analysed. We conclude that the functional imprinting status of IGF2 during postnatal liver development appears to be promoter/enhancer-specific and either partly or completely independent of H19.
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  • Gomez-Cabrero, D, et al. (författare)
  • Comment on "Epigenetics in the pathogenesis of RA"
  • 2017
  • Ingår i: Seminars in immunopathology. - : Springer Science and Business Media LLC. - 1863-2300 .- 1863-2297. ; 39:4, s. 421-422
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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