Massimo Porta1, Cristina Amione2, Federica Barutta2, Paolo Fornengo2, Stefano Merlo2, Gabriella Gruden2, Luigi Albano3, Marco Ciccarelli3, Paola Ungaro3, Marilena Durazzo2, Francesco Beguinot3,4, Paola Berchialla5, Franco Cavallo6, Marina Trento2. 1. Department of Medical Sciences, Laboratory of Clinical Pedagogy, University of Turin, Turin, Italy. massimo.porta@unito.it. 2. Department of Medical Sciences, Laboratory of Clinical Pedagogy, University of Turin, Turin, Italy. 3. National Research Council, URT of the Institute of Experimental Endocrinology Oncology "G. Salvatore", Naples, Italy. 4. Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy. 5. Department of Clinical and Biological Sciences, University of Turin, Turin, Italy. 6. Department of Public Health and Paediatric Sciences, University of Turin, Turin, Italy.
Abstract
PURPOSE: We examined the expression of a panel of epigenetic enzymes catalyzing histone tails post-transcriptional modifications, together with effectors of metabolic and inflammatory alterations, in type 2 diabetes. METHODS: Cross-sectional, case-control study of 21 people with type 2 diabetes and 21 matched controls. Total RNA was extracted from white cells and reverse transcribed. PCR primer assays for 84 key genes encoding enzymes known to modify genomic DNA and histones were performed. Western blot was performed on lysates using primary antibodies for abnormally expressed enzymes. Hormones and cytokines were measured by multiplex kits. A Bayesian network was built to investigate the relationships between epigenetic, cytokine, and endocrine variables. RESULTS: Co-activator-associated aRginine Methyltransferase 1 (CARM1) expression showed a five-fold higher median value, matched by higher protein levels, among patients who also had increased GIP, IL-4, IL-7, IL-13, IL-17, FGF basic, G-CSF, IFN-γ, and TNFα and decreased IP-10. In a Bayesian network approach, CARM1 expression showed a conditional dependence on diabetes, but was independent of all other variables nor appeared to influence any. CONCLUSIONS: Increased CARM1 expression in type 2 diabetes suggests that epigenetic mechanisms are altered in human diabetes. The impact of lifestyle and pharmacological treatment on regulation of this enzyme should be further investigated.
PURPOSE: We examined the expression of a panel of epigenetic enzymes catalyzing histone tails post-transcriptional modifications, together with effectors of metabolic and inflammatory alterations, in type 2 diabetes. METHODS: Cross-sectional, case-control study of 21 people with type 2 diabetes and 21 matched controls. Total RNA was extracted from white cells and reverse transcribed. PCR primer assays for 84 key genes encoding enzymes known to modify genomic DNA and histones were performed. Western blot was performed on lysates using primary antibodies for abnormally expressed enzymes. Hormones and cytokines were measured by multiplex kits. A Bayesian network was built to investigate the relationships between epigenetic, cytokine, and endocrine variables. RESULTS:Co-activator-associated aRginine Methyltransferase 1 (CARM1) expression showed a five-fold higher median value, matched by higher protein levels, among patients who also had increased GIP, IL-4, IL-7, IL-13, IL-17, FGF basic, G-CSF, IFN-γ, and TNFα and decreased IP-10. In a Bayesian network approach, CARM1 expression showed a conditional dependence on diabetes, but was independent of all other variables nor appeared to influence any. CONCLUSIONS: Increased CARM1 expression in type 2 diabetes suggests that epigenetic mechanisms are altered in humandiabetes. The impact of lifestyle and pharmacological treatment on regulation of this enzyme should be further investigated.
Entities:
Keywords:
CARM1; Epigenetics; Histone methylation; Type 2 diabetes
Authors: Megan K Mulligan; Igor Ponomarev; Robert J Hitzemann; John K Belknap; Boris Tabakoff; R Adron Harris; John C Crabbe; Yuri A Blednov; Nicholas J Grahame; Tamara J Phillips; Deborah A Finn; Paula L Hoffman; Vishwanath R Iyer; George F Koob; Susan E Bergeson Journal: Proc Natl Acad Sci U S A Date: 2006-04-17 Impact factor: 11.205
Authors: Fabio Marino; Geert P M Mommen; Anita Jeko; Hugo D Meiring; Jacqueline A M van Gaans-van den Brink; Richard A Scheltema; Cécile A C M van Els; Albert J R Heck Journal: J Proteome Res Date: 2016-08-25 Impact factor: 4.466