title: Histone h1.3 suppresses h19 noncoding RNA expression and cell growth of ovarian cancer cells.
abstract: Ovarian cancer is a deadly gynecologic malignancy for which novel biomarkers and therapeutic targets are imperative for improving survival. Previous studies have suggested the expression pattern of linker histone variants as potential biomarkers for ovarian cancer. To investigate the role of histone H1 in ovarian cancer cells, we characterize individual H1 variants and overexpress one of the major somatic H1 variants, H1.3, in the OVCAR-3 epithelial ovarian cancer cell line. We find that overexpression of H1.3 decreases the growth rate and colony formation of OVCAR-3 cells. We identify histone H1.3 as a specific repressor for the noncoding oncogene H19. Overexpression of H1.3 suppresses H19 expression, and knockdown of H1.3 increases its expression in multiple ovarian epithelial cancer cell lines. Furthermore, we demonstrate that histone H1.3 overexpression leads to increased occupancy of H1.3 at the H19 regulator region encompassing the imprinting control region (ICR), concomitant with increased DNA methylation and reduced occupancy of the insulator protein CTCF at the ICR. Finally, we demonstrate that H1.3 overexpression and H19 knockdown synergistically decrease the growth rate of ovarian cancer cells. Our findings suggest that H1.3 dramatically inhibits H19 expression, which contributes to the suppression of epithelial ovarian carcinogenesis.
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, Georgia. The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Medrzycki
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, Georgia. The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia.
authors.forename: Yunzhe
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Weijia
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, Georgia. The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia.
authors.forename: Kaixiang
authors.initials: K
authors.lastname: Cao
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, Georgia. The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia.
authors.forename: Chenyi
authors.initials: C
authors.lastname: Pan
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lailler
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, Georgia. The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia.
authors.forename: John F
authors.initials: JF
authors.lastname: McDonald
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Bouhassira
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, Georgia. The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia. Yuhong.fan@biology.gatech.edu.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Fan
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000502:physiology*; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology*; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
chemical_list: C094335:H19 long non-coding RNA; D006657:Histones; D062085:RNA, Long Noncoding