title: Genome-wide analysis distinguishes hyperglycemia regulated epigenetic signatures of primary vascular cells.
abstract: Emerging evidence suggests that poor glycemic control mediates post-translational modifications to the H3 histone tail. We are only beginning to understand the dynamic role of some of the diverse epigenetic changes mediated by hyperglycemia at single loci, yet elevated glucose levels are thought to regulate genome-wide changes, and this still remains poorly understood. In this article we describe genome-wide histone H3K9/K14 hyperacetylation and DNA methylation maps conferred by hyperglycemia in primary human vascular cells. Chromatin immunoprecipitation (ChIP) as well as CpG methylation (CpG) assays, followed by massive parallel sequencing (ChIP-seq and CpG-seq) identified unique hyperacetylation and CpG methylation signatures with proximal and distal patterns of regionalization associative with gene expression. Ingenuity knowledge-based pathway and gene ontology analyses indicate that hyperglycemia significantly affects human vascular chromatin with the transcriptional up-regulation of genes involved in metabolic and cardiovascular disease. We have generated the first installment of a reference collection of hyperglycemia-induced chromatin modifications using robust and reproducible platforms that allow parallel sequencing-by-synthesis of immunopurified content. We uncover that hyperglycemia-mediated induction of genes and pathways associated with endothelial dysfunction occur through modulation of acetylated H3K9/K14 inversely correlated with methyl-CpG content.
authors: Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia.
authors: Luciano
authors: L
authors: Pirola
authors: Aneta
authors: A
authors: Balcerczyk
authors: Richard W
authors: RW
authors: Tothill
authors: Izhak
authors: I
authors: Haviv
authors: Antony
authors: A
authors: Kaspi
authors: Sebastian
authors: S
authors: Lunke
authors: Mark
authors: M
authors: Ziemann
authors: Tom
authors: T
authors: Karagiannis
authors: Stephen
authors: S
authors: Tonna
authors: Adam
authors: A
authors: Kowalczyk
authors: Bryan
authors: B
authors: Beresford-Smith
authors: Geoff
authors: G
authors: Macintyre
authors: Ma
authors: M
authors: Kelong
authors: Zhang
authors: Z
authors: Hongyu
authors: Jingde
authors: J
authors: Zhu
authors: Assam
authors: A
authors: El-Osta
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D001011:Aorta / Q000166:cytology*; D002478:Cells, Cultured; D002877:Chromosomes, Human; D018899:CpG Islands; D019175:DNA Methylation; D003920:Diabetes Mellitus / Q000235:genetics; D003925:Diabetic Angiopathies / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D061251:Primary Cell Culture; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D000123:Acetyltransferases