title: Epigenetic drift towards histone modifications regulates CAV1 gene expression in colon cancer.
abstract: BACKGROUND
  Caveolin-1 (CAV1) is an important structural component of cellular caveolae involved in cell signaling. CAV1 gene on/off regulatory mechanism in multiple diseases, including cancer is not clearly understood. The tumor suppressor versus oncogene paradox of CAV1 during tumor development tempted us to investigate the role for the epigenetic drift of CAV1 gene regulation.
  
  
  METHODS
  We have analyzed CAV1 gene expression and associated epigenetic marks (DNA methylation and histone 3 modifications) in the CAV1 promoter in two colon cancer cell lines, under treatment with well established epigenetic modulators, AZA, SAM, TSA and SFN at varying concentrations. CAV1 gene promoter DNA methylation and histone modifications were analyzed by DNA methylation specific PCR, bisulphite modification of DNA and ChIP analyses following PCR respectively.
  
  
  RESULTS
  Ectopic expression of CAV1 by epigenetic modulators inhibits colon cancer cell growth. CAV1 promoter DNA remains unmethylated before and after treatment with epigenetic modulators, which confirmed that DNA methylation is not the regulator of CAV1 expression in colon cancer. There was enrichment of H3K4me3 and H3K9AcS10P and depletion of H3K9me3 modifications around the CAV1 promoter.
  
  
  CONCLUSIONS
  Our data provides novel insight into the regulation of CAV1 gene by histone H3 modifications and enhance the amplitude of the cancer epigenome.
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, National Institute of Technology, Rourkela, Odisha 769008, India; Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008, India.
authors.forename: Moonmoon
authors.initials: M
authors.lastname: Deb
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, National Institute of Technology, Rourkela, Odisha 769008, India; Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008, India.
authors.forename: Dipta
authors.initials: D
authors.lastname: Sengupta
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, National Institute of Technology, Rourkela, Odisha 769008, India; Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008, India.
authors.forename: Swayamsiddha
authors.initials: S
authors.lastname: Kar
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, National Institute of Technology, Rourkela, Odisha 769008, India; Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008, India.
authors.forename: Sandip Kumar
authors.initials: SK
authors.lastname: Rath
authors.affiliation: Drs. Tribedi & Roy Diagnostic Laboratory, 93, Park Street, Kolkata 700 016, India.
authors.forename: Subhendu
authors.initials: S
authors.lastname: Roy
authors.affiliation: Department of Surgery, Calcutta National Medical College, Kolkata 7000 014, India.
authors.forename: Goutam
authors.initials: G
authors.lastname: Das
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, National Institute of Technology, Rourkela, Odisha 769008, India; Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008, India. Electronic address: samirp@nitrkl.ac.in.
authors.forename: Samir Kumar
authors.initials: SK
authors.lastname: Patra
mesh_terms: D017209:Apoptosis; D051242:Caveolin 1 / Q000235:genetics*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D044127:Epigenesis, Genetic / Q000187:drug effects; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D006657:Histones
keywords: Caveolin1; Colon cancer; DNA methylation; Epigenetics; Histone 3 lysine 4 trimethylation; Histone 3 lysine 9 trimethylation