Post-GWAS functional studies reveal an RA-associated CD40-induced NF-kB signal transduction and transcriptional regulation network targeted by class II HDAC inhibitors.

ABSTRACT: Currently, it remains difficult to identify which single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) are functional and how various functional SNPs (fSNPs) interact and contribute to disease susceptibility. GWAS have identified a CD40 locus that is associated with rheumatoid arthritis (RA). We previously used two techniques developed in our laboratory, single nucleotide polymorphism-next-generation sequencing (SNP-seq) and flanking restriction enhanced DNA pulldown-mass spectrometry (FREP-MS), to determine that the RA risk gene RBPJ regulates CD40 expression via a fSNP at the RA-associated CD40 locus. In the present work, by applying the same approach, we report the identification of six proteins that regulate RBPJ expression via binding to two fSNP

SUBMITTER: Zou M 

PROVIDER: S-EPMC8161515 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature