title: Genes Frequently Coexpressed with Hoxc8 Provide Insight into the Discovery of Target Genes.
abstract: Identifying Hoxc8 target genes is at the crux of understanding the Hoxc8-mediated regulatory networks underlying its roles during development. However, identification of these genes remains difficult due to intrinsic factors of Hoxc8, such as low DNA binding specificity, context-dependent regulation, and unknown cofactors. Therefore, as an alternative, the present study attempted to test whether the roles of Hoxc8 could be inferred by simply analyzing genes frequently coexpressed with Hoxc8, and whether these genes include putative target genes. Using archived gene expression datasets in which Hoxc8 was differentially expressed, we identified a total of 567 genes that were positively coexpressed with Hoxc8 in at least four out of eight datasets. Among these, 23 genes were coexpressed in six datasets. Gene sets associated with extracellular matrix and cell adhesion were most significantly enriched, followed by gene sets for skeletal system development, morphogenesis, cell motility, and transcriptional regulation. In particular, transcriptional regulators, including paralogs of Hoxc8, known Hox co-factors, and transcriptional remodeling factors were enriched. We randomly selected Adam19, Ptpn13, Prkd1, Tgfbi, and Aldh1a3, and validated their coexpression in mouse embryonic tissues and cell lines following TGF-β2 treatment or ectopic Hoxc8 expression. Except for Aldh1a3, all genes showed concordant expression with that of Hoxc8, suggesting that the coexpressed genes might include direct or indirect target genes. Collectively, we suggest that the coexpressed genes provide a resource for constructing Hoxc8-mediated regulatory networks.
authors.affiliation: Department of Anatomy, Embryology Lab., Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.
authors.forename: Ruthala
authors.initials: R
authors.lastname: Kalyani
authors.affiliation: Department of Anatomy, Embryology Lab., Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Embryology Lab., Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.
authors.forename: Hyehyun
authors.initials: H
authors.lastname: Min
authors.affiliation: Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
authors.forename: Heejei
authors.initials: H
authors.lastname: Yoon
authors.affiliation: Department of Anatomy, Embryology Lab., Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.
authors.forename: Myoung Hee
authors.initials: MH
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D030541:Databases, Genetic; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C489816:Hoxc8 protein, mouse; D014157:Transcription Factors
keywords: Hox genes; coexpressed genes; in silico analysis; pattern formation; vertebrate development