ChIP-seq analysis of histone H3K9 trimethylation in peripheral blood mononuclear cells of membranous nephropathy patients

Abstract

Membranous nephropathy (MN), characterized by the presence of diffuse thickening of the glomerular basement membrane and subepithelial in situ immune complex disposition, is the most common cause of idiopathic nephrotic syndrome in adults, with an incidence of 5-10 per million per year. A number of studies have confirmed the relevance of several experimental insights to the pathogenesis of human MN, but the specific biomarkers of MN have not been fully elucidated. As a result, our knowledge of the alterations in histone methylation in MN is unclear. We used chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) to analyze the variations in a methylated histone (H3K9me3) in peripheral blood mononuclear cells from 10 MN patients and 10 healthy subjects. There were 108 genes with significantly different expression in the MN patients compared with the normal controls. In MN patients, significantly increased activity was seen in 75 H3K9me3 genes, and decreased activity was seen in 33, compared with healthy subjects. Five positive genes, DiGeorge syndrome critical region gene 6 (DGCR6), sorting nexin 16 (SNX16), contactin 4 (CNTN4), baculoviral IAP repeat containing 3 (BIRC3), and baculoviral IAP repeat containing 2 (BIRC2), were selected and quantified. There were alterations of H3K9me3 in MN patients. These may be candidates to help explain pathogenesis in MN patients. Such novel findings show that H3K9me3 may be a potential biomarker or promising target for epigenetic-based MN therapies.

GWAS and transcriptional analysis prioritize ITPR1 and CNTN4 for a serum uric acid 3p26 QTL in Mexican Americans

“…The variants in this gene are associated with developmental delays and mental retardation and may be relevant to autism-related spectrum disorders [ 30 – 32 ]. Disruption of CNTN4 is also thought to cause cognitive defects [ 33 ]. Our study showed strong association of SUA concentrations with CNTN4 SNPs.…”

Important biological information uncovered in previously unaligned reads from chromatin immunoprecipitation experiments (ChIP-Seq)

“…The combination of computational analyses and experimental validation revealed that a high proportion of unmapped ChIP-Seq reads were mappable after being subjected to a taxonomic classification and subsequent remapping using SHRiMP, a short read aligner capable of mapping reads to highly polymorphic regions of the genome. We discovered that these previously ignored reads, also reported in ChIP-Seq experiments conducted with various modified histones 27 28 29 30 harbor key information that showed novel aspects important for the reconstruction of gene regulatory grids. By focusing on the human TAL1 TF, a set of previously unaligned reads were shown to have mappable properties and have been used for identification and validation of novel TAL1 binding sites, revealing important characteristics on how this TF can regulate cell fate determination, apoptosis, and potential novel role in sensory perception.…”

Differential methylation as a diagnostic biomarker of rare renal diseases: a systematic review

“…Therefore, studying epigenetic features, such as DNA methylation, may offer new insights by providing a mechanism to understand how each individual’s genome interacts with their environment through the epigenome. However, this review highlights that only a small number of studies have been reported researching differential methylation in rare renal diseases: IgAN [48–50]ADPKD [51–53]Rare diseases causing proteinuria including membranous nephropathy [54, 55] and focal segmental glomerulosclerosis (FSGS) [56–59]Congenital renal agenesis [60]…”

“…Rare diseases causing proteinuria including membranous nephropathy [54, 55] and focal segmental glomerulosclerosis (FSGS) [56–59]…”

“…Increased H3K4me3 was found to exacerbate proteinuria in membranous nephropathy [55], with murine models showing that targeting shRNA against an H3K4 methyltransferase, MLL3, alleviated proteinuria. H3K9me3 alterations were also found to be a biomarker of membranous nephropathy compared to normal control patients [54]. FSGS, included in the RaDaR elgibility criteria, is a condition describing sclerosis of the kidney, with a variety of causes.…”