Pubmed-entry ::= {
  pmid 21903580,
  medent {
    em std {
      year 2011,
      month 10,
      day 24
    },
    cit {
      title {
        name "5-aza-2'-deoxycytidine activates iron uptake and heme
 biosynthesis by increasing c-Myc nuclear localization and binding to the
 E-boxes of transferrin receptor 1 (TfR1) and ferrochelatase (Fech) genes."
      },
      authors {
        names ml {
          "Ning B",
          "Liu G",
          "Liu Y",
          "Su X",
          "Anderson GJ",
          "Zheng X",
          "Chang Y",
          "Guo M",
          "Liu Y",
          "Zhao Y",
          "Nie G"
        },
        affil str "Chinese Academy of Sciences Key Laboratory for Biological
 Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and
 Technology, 11 Zhongguancun Beiyitiao, Beijing 100190, China."
      },
      from journal {
        title {
          iso-jta "J. Biol. Chem.",
          ml-jta "J Biol Chem",
          issn "1083-351X",
          name "The Journal of biological chemistry"
        },
        imp {
          date std {
            year 2011,
            month 10,
            day 28
          },
          volume "286",
          issue "43",
          pages "37196-37206",
          language "eng",
          pubstatus ppublish,
          history {
            {
              pubstatus aheadofprint,
              date std {
                year 2011,
                month 9,
                day 7
              }
            },
            {
              pubstatus other,
              date std {
                year 2011,
                month 9,
                day 10,
                hour 6,
                minute 0
              }
            },
            {
              pubstatus pubmed,
              date std {
                year 2011,
                month 9,
                day 10,
                hour 6,
                minute 0
              }
            },
            {
              pubstatus medline,
              date std {
                year 2011,
                month 12,
                day 16,
                hour 6,
                minute 0
              }
            },
            {
              pubstatus other,
              date std {
                year 2012,
                month 10,
                day 28,
                hour 0,
                minute 0
              }
            }
          }
        }
      },
      ids {
        pii "M111.258129",
        doi "10.1074/jbc.M111.258129",
        pubmed 21903580,
        other {
          db "pmc",
          tag str "PMC3199467"
        }
      }
    },
    abstract "The hypomethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR) and
 its derivatives have been successfully used for the treatment of
 myelodysplastic syndromes, and they frequently improve the anemia that
 usually accompanies these disorders. However, the molecular mechanisms
 underlying this action remain poorly understood. In this study, we used two
 erythroid models, murine erythroid leukemia cells and erythroid burst-forming
 unit-derived erythroblasts, to show that 5-aza-CdR induced erythroid
 differentiation and increased the expression of transferrin receptor 1 (TfR1)
 and ferrochelatase (Fech), thereby increasing iron uptake and heme
 biosynthesis. We have identified new regulatory E-boxes that lie outside of
 CpG islands in the TfR1 and Fech promoters, and the methylation status of
 these sites can be altered by 5-aza-CdR treatment. This in turn altered the
 binding of the transcription factor c-Myc to these promoter elements.
 Furthermore, 5-aza-CdR promoted the nuclear translocation of c-Myc and its
 binding to Max to form functional complexes. The coordinated actions of
 5-aza-CdR on the methylation status of the target genes and in stimulating
 the nuclear translocation of c-Myc provide new molecular insights into the
 regulation of E-boxes and explain, at least in part, the increased erythroid
 response to 5-aza-CdR treatment.",
    mesh {
      {
        term "Active Transport, Cell Nucleus",
        qual {
          {
            subh "drug effects"
          },
          {
            subh "physiology"
          }
        }
      },
      {
        term "Animals"
      },
      {
        term "Azacitidine",
        qual {
          {
            mp TRUE,
            subh "analogs & derivatives"
          },
          {
            subh "pharmacology"
          }
        }
      },
      {
        term "Basic Helix-Loop-Helix Leucine Zipper Transcription Factors",
        qual {
          {
            subh "genetics"
          },
          {
            subh "metabolism"
          }
        }
      },
      {
        term "Cell Line, Tumor"
      },
      {
        term "Cell Nucleus",
        qual {
          {
            mp TRUE,
            subh "metabolism"
          }
        }
      },
      {
        term "CpG Islands",
        qual {
          {
            subh "physiology"
          }
        }
      },
      {
        term "Enzyme Inhibitors",
        qual {
          {
            mp TRUE,
            subh "pharmacology"
          }
        }
      },
      {
        term "Erythroid Cells"
      },
      {
        term "Ferrochelatase",
        qual {
          {
            mp TRUE,
            subh "metabolism"
          }
        }
      },
      {
        term "Heme",
        qual {
          {
            mp TRUE,
            subh "biosynthesis"
          }
        }
      },
      {
        term "Humans"
      },
      {
        term "Iron",
        qual {
          {
            mp TRUE,
            subh "metabolism"
          }
        }
      },
      {
        term "Mice"
      },
      {
        term "Proto-Oncogene Proteins c-myc",
        qual {
          {
            mp TRUE,
            subh "metabolism"
          }
        }
      },
      {
        term "Receptors, Transferrin",
        qual {
          {
            mp TRUE,
            subh "metabolism"
          }
        }
      },
      {
        term "Response Elements",
        qual {
          {
            mp TRUE,
            subh "physiology"
          }
        }
      }
    },
    substance {
      {
        type nameonly,
        name "Basic Helix-Loop-Helix Leucine Zipper Transcription Factors"
      },
      {
        type nameonly,
        name "Enzyme Inhibitors"
      },
      {
        type nameonly,
        name "Myc protein, mouse"
      },
      {
        type nameonly,
        name "Proto-Oncogene Proteins c-myc"
      },
      {
        type nameonly,
        name "Receptors, Transferrin"
      },
      {
        type nameonly,
        name "Tfrc protein, mouse"
      },
      {
        type cas,
        cit "137468-70-3",
        name "Max protein, mouse"
      },
      {
        type cas,
        cit "14875-96-8",
        name "Heme"
      },
      {
        type cas,
        cit "2353-33-5",
        name "decitabine"
      },
      {
        type cas,
        cit "320-67-2",
        name "Azacitidine"
      },
      {
        type cas,
        cit "7439-89-6",
        name "Iron"
      },
      {
        type ec,
        cit "4.99.1.1",
        name "Ferrochelatase"
      }
    },
    pmid 21903580,
    pub-type {
      "Journal Article",
      "Research Support, Non-U.S. Gov't"
    },
    status medline
  }
}

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