DNA methylation profiling of the X chromosome reveals an aberrant demethylation on CXCR3 promoter in primary biliary cirrhosis

• DOI: 10.1186/s13148-015-0098-9
• Publication Date: 2015-07-06T10:14:00Z
• Authors: Ana Lleo; Weici Zhang; Ming Zhao; Yixin Tan; Francesca Bernuzzi; Bochen Zhu; Qian Liu; Qiqun Tan; Federica Malinverno; Luca Valenti; Tingting Jiang; Lina Tan; Wei Liao; Ross Coppel; Pietro Invernizzi; Qianjin Lu; David H. Adams; M. Eric Gershwin
• Keywords: Primary Biliary Cirrhosis; DNA demethylation; Epigenomics

Although the etiology of primary biliary cirrhosis (PBC) remains enigmatic, there are several pieces data supporting thesis that a strong genetic predisposition and environmental factors interact to produce selective loss tolerance. The striking female predominance PBC has suggested this sex may be secondary epigenetic alterations on X chromosome. In present study, we rigorously defined chromosome methylation profile CD4, CD8, CD14 cells from 30 patients controls. Genomic DNA sorted subpopulations was isolated, sonicated, immunoprecipitated for analysis methylation. All products were hybridized custom-tiled four-plex array containing 27,728 CpG islands annotated by UCSC 22,532 well-characterized RefSeq promoter regions. Furthermore, bisulfite sequencing then used validation subsequent group independent samples Thence, expression levels selected X-linked genes evaluated quantitative real-time PCR with cDNA all subjects.We report herein total 20, 15, 19 distinct gene promoters reflected significant difference in CD4+ T, CD8+ CD14+ PBC. Interestingly, hypermethylation FUNDC2 T demethylation CXCR3 cells, which inversely correlated early-stage patients.Our provides set alteration likely indicators autoimmunity emphasizes role natural history