title: Truncation of histone H2A's C-terminal tail, as is typical for Ni(II)-assisted specific peptide bond hydrolysis, has gene expression altering effects.
abstract: Nickel(II), capable of transforming cells and causing tumors in humans and animals, has been previously shown by us to mediate hydrolytic truncation of histone H2A's C-terminal tail by 8 amino acids in both cell-free and cell culture systems. Since H2A's C-tail is involved in maintaining chromatin structure, such truncation might alter this structure and affect gene expression. To test the latter possibility, we transfected cultured T-REx 293 human embryonic kidney cells with plasmids expressing either wild type (wt) or truncated (q) histone H2A proteins, which were either untagged or N-terminally tagged with fluorescent proteins. Each histone variant was found to be incorporated into chromatin at 24 and 48 hr post-transfection. Cells transfected with the untagged plasmids were tested for gene expression by microarray and real-time PCR. Evaluation of the results for over 21,000 genes using the multidimensional scaling and hierarchical clustering methods revealed significant differences in expression of numerous genes between the q-H2A and wt-H2A transfectants. Many of the differentially expressed genes, including BAZ2A, CLDN18, CYP51A1, GFR, GIPC2, HMGB1, IRF7, JAK3, PSIP1, and VEGF, are cancer-related genes. The results thus demonstrate the potential of q-H2A to contribute to the process of carcinogenesis through epigenetic mechanisms.
authors: Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
authors: Aldona A
authors: AA
authors: Karaczyn
authors: Robert Y S
authors: RY
authors: Cheng
authors: Gregory S
authors: GS
authors: Buzard
authors: James
authors: J
authors: Hartley
authors: Dominic
authors: D
authors: Esposito
authors: Kazimierz S
authors: KS
authors: Kasprzak
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D016000:Cluster Analysis; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D009369:Neoplasms / Q000209:etiology; D009532:Nickel / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
chemical_list: D006657:Histones; D011993:Recombinant Fusion Proteins; D009532:Nickel