title: hDREF regulates cell proliferation and expression of ribosomal protein genes.
abstract: Although ribosomal proteins (RPs) are essential cellular constituents in all living organisms, mechanisms underlying regulation of their gene expression in mammals remain unclear. We have established that 22 out of 79 human RP genes contain sequences similar to the human DREF (DNA replication-related element-binding factor; hDREF) binding sequence (hDRE) within 200-bp regions upstream of their transcriptional start sites. Electrophoretic gel mobility shift assays and chromatin immunoprecipitation analysis indicated that hDREF binds to hDRE-like sequences in the RP genes both in vitro and in vivo. In addition, transient luciferase assays revealed that hDRE-like sequences act as positive elements for RP gene transcription and cotransfection of an hDREF-expressing plasmid was found to stimulate RP gene promoter activity. Like that of hDREF, expression of RP genes is increased during the late G(1) to S phases, and depletion of hDREF using short hairpin RNA-mediated knockdown decreased RP gene expression and cell proliferation in normal human fibroblasts. Knockdown of the RPS6 gene also resulted in impairment of cell proliferation. These data suggest that hDREF is an important transcription factor for cell proliferation which plays roles in cell cycle-dependent regulation of a number of RP genes.
authors.affiliation: Graduate School of Life Science, University of Hyogo, Kamigori, Hyogo 678-1297, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamashita
authors.forename: Yukako
authors.initials: Y
authors.lastname: Sano
authors.forename: Yuka
authors.initials: Y
authors.lastname: Adachi
authors.forename: Yuma
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Osada
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Osumi
authors.forename: Fumiko
authors.initials: F
authors.lastname: Hirose
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D049109:Cell Proliferation; D029721:Drosophila Proteins; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: C099494:Dref protein, Drosophila; D029721:Drosophila Proteins; D012269:Ribosomal Proteins; D014157:Transcription Factors; C518505:ZBED1 protein, human