title: Reduced Histone H3 Acetylation in CD4(+) T Lymphocytes: Potential Mechanism of Latent Autoimmune Diabetes in Adults.
abstract: Aims. Latent autoimmune diabetes in adults (LADA) is the result of gene-environment interactions. Histone acetylation regulates gene expression and maybe interpret how environmental factors modify LADA. Hence, we studied the histone acetylation patterns in CD4(+) T lymphocytes from LADA patients. Methods. Blood CD4(+) T lymphocytes from 28 patients with LADA and 28 healthy controls were obtained to detect histone H3 acetylation and H4 acetylation. The gene expression of histone acetyltransferases (P300 and CREBBP) and histone deacetylases (HDAC1, HDAC2, and HDAC7) was measured by real-time polymerase chain reaction (RT-PCR). Results. Compared to healthy controls, reduced global H3 acetylation was observed in LADA patients' CD4(+) T lymphocytes (P < 0.05). Global level of H4 acetylation was not statistically different. Among LADA, CD4(+) T lymphocytes H3 acetylation was associated with glycosylated hemoglobin (HbA1c) and GADA titer. Compared to healthy controls, the expression of histone acetyltransferases CREBBP in LADA patients was downregulated, and the expression of histone deacetylases HDAC1 and HDAC7 was upregulated. Conclusion. A concerted downregulation of histone H3 acetylation was found in CD4(+) T lymphocytes of LADA patients, and this might provide evidence of a novel epigenetic explanation for the pathogenesis of LADA and its complications.
authors.affiliation: Department of Endocrinology, Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, China.
authors.forename: Xi-Yu
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Department of Surgery, Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, China.
authors.forename: Jiang-Feng
authors.initials: JF
authors.lastname: Xu
mesh_terms: D000107:Acetylation; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D015536:Down-Regulation; D005260:Female; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011499:Protein Processing, Post-Translational
chemical_list: D006657:Histones; D006655:Histone Deacetylases
references.citation: Genes Cancer. 2015 May;6(5-6):184-213
references.pmid: 26124919
references.citation: Clin Immunol. 2014 Jul;153(1):23-30
references.pmid: 24704576
references.citation: J Biol Chem. 2012 May 11;287(20):16335-45
references.pmid: 22431725
references.citation: Diabetologia. 2015 Mar;58(3):443-55
references.pmid: 25481708
references.citation: Diabetes. 2015 Feb;64(2):631-42
references.pmid: 25204977
references.citation: Lancet. 2014 Mar 22;383(9922):1084-94
references.pmid: 24315621
references.citation: Diabetes. 2013 Feb;62(2):543-50
references.pmid: 23086039
references.citation: Curr Diab Rep. 2014;14(11):550
references.pmid: 25189437
references.citation: Biochim Biophys Acta. 2015 Jan;1852(1):34-46
references.pmid: 25446993
references.citation: Immunol Cell Biol. 2015 Mar;93(3):271-6
references.pmid: 25776989
references.citation: Genes (Basel). 2015 Jul 15;6(3):607-21
references.pmid: 26184324
references.citation: J Med Chem. 2015 Feb 26;58(4):1596-629
references.pmid: 25406853
references.citation: Diabetes. 2014 May;63(5):1748-62
references.pmid: 24458354
references.citation: J Autoimmun. 2013 Dec;47:83-93
references.pmid: 24090977
references.citation: J Physiol Biochem. 2015 Mar;71(1):89-98
references.pmid: 25666660
references.citation: BMC Endocr Disord. 2015;15:1
references.pmid: 25572256
references.citation: Biochim Biophys Acta. 2014 Dec;1839(12):1416-32
references.pmid: 24859458
references.citation: Nucleus. 2013 Sep-Oct;4(5):343-8
references.pmid: 23941995
references.citation: Diabet Med. 2015 Jul;32(7):843-52
references.pmid: 25601320
references.citation: Endocr Pract. 2006 Jan-Feb;12 Suppl 1:34-41
references.pmid: 16627378