ETS family protein GABP is a novel co-factor strongly associated with genomic YY1 binding sites in various cell lines

Abstract

The Yin Yang 1 (YY1) protein is a ubiquitously expressed transcription factor involved in gene activation, repression, and genomic imprinting. Recent studies have revealed genome-wide target loci of YY1 in different cell types using chromatin immunoprecipitation with massively parallel DNA sequencing (ChIP-seq). However, it is unclear how the same YY1 controls different sets of genes in various cell types. To unveil potential co-factors of YY1, we reanalyzed YY1 and CTCF ChIP-seq data sets generated by the ENCODE consortium for various cell lines. As reported previously, CCCTC-binding factor (CTCF) is one of the most frequently associated co-factors around genomic YY1 binding sites in all cases. When it comes to strong YY1 binding sites, however, binding motifs of the E26 transformation-specific (ETS) family proteins are significantly prevalent. Indeed, meta-analysis of the ETS transcription factor GABP ChIP-seq performed in various cell types confirmed the strong genomic association between YY1 and GABP. Particularly, genes around common YY1 binding sites that are defined as invariable strong binding across cell lines were significantly associated with GABP in almost all cell types examined. In addition, the association between YY1 and GABP is strongly conserved in primate genomes such as chimpanzee, orangutan and baboon. Gene ontology analysis revealed that the YY1-GABP co-regulated genes are significantly associated with Alzheimer’s disease in human. Overall, the meta-analysis of available YY1, CTCF, and GABP ChIP-seq data showed a novel genomic association between YY1 and GABP, suggesting that the YY1–GABP co-regulatory network is common across multiple cell types.