title: HP1a/KDM4A is involved in the autoregulatory loop of the oncogene gene c-Jun.
abstract: The proto-oncogene c-Jun plays crucial roles in tumorigenesis, and its aberrant expression has been implicated in many cancers. Previous studies have shown that the c-Jun gene is positively autoregulated by its product. Notably, it has also been reported that c-Jun proteins are enriched in its gene body region. However, the role of c-Jun proteins in its gene body region has yet to be uncovered. HP1a is an evolutionarily conserved heterochromatin-associated protein, which plays an essential role in heterochromatin-mediated gene silencing. Interestingly, accumulating evidence shows that HP1a is also localized to euchromatic regions to positively regulate gene transcription. However, the underlying mechanism has not been defined. In this study, we demonstrate that HP1a is involved in the positive autoregulatory loop of the Jra gene, the c-Jun homolog in Drosophila. Jra recruits the HP1a/KDM4A complex to its gene body region upon osmotic stress to reduce H3K36 methylation levels and disrupt H3K36 methylation-dependent histone deacetylation, resulting in high levels of histone acetylation in the Jra gene body region, thus promoting gene transcription. These results not only expand our knowledge toward the mechanism of c-Jun regulation, but also reveal the mechanism by which HP1a exerts its positive regulatory function in gene expression.
authors.affiliation: a College of Life Sciences; Hebei United University ; Tangshan , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Daoyong
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000107:Acetylation; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006570:Heterochromatin / Q000235:genetics; D056466:Histone Demethylases / Q000235:genetics; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D008745:Methylation; D009997:Osmotic Pressure; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D018808:Transcription Factor AP-1
chemical_list: D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D006570:Heterochromatin; D056466:Histone Demethylases; D006657:Histones; D056484:Jumonji Domain-Containing Histone Demethylases; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun; C000605629:Jra protein, Drosophila; D018808:Transcription Factor AP-1; C000715470:MAS1 protein, human; C494424:KDM4A protein, human
keywords: AP-1, Activating Protein 1; HP1a, Heterochromatin protein 1a; Jra, Jun-related antigen; KDM4A, lysine-specific demethylase 4A; H3K36 methylation; HP1a; Jra; KDM4A; osmotic stress