Sumoylation of p45/NF-E2: Nuclear positioning and transcriptional activation of the mammalian β-like globin gene locus

Yu Chiau Shyu, Tung Liang Lee, Chun Yuan Ting, Shau Ching Wen, Lie Jiau Hsieh, Yueh Chun Li, Jau Lang Hwang, Chyi Chyang Lin, C. K James Shen

研究成果: 雜誌貢獻文章

23 引文 斯高帕斯(Scopus)

摘要

NF-E2 is a transcription activator for the regulation of a number of erythroid- and megakaryocytic lineage-specific genes. Here we present evidence that the large subunit of mammalian NF-E2, p45, is sumoylated in vivo in human erythroid K562 cells and in mouse fetal liver. By in vitro sumoylation reaction and DNA transfection experiments, we show that the sumoylation occurs at lysine 368 (K368) of human p45/NF-E2. Furthermore, p45 sumoylation enhances the transactivation capability of NF-E2, and this is accompanied by an increase of the NF-E2 DNA binding affinity. More interestingly, we have found that in K562 cells, the β-globin gene loci in the euchromatin regions are predominantly colocalized with the nuclear bodies promyelocytic leukemia protein (PML) oncogenic domains that are enriched with the PML, SUMO-1, RNA polymerase II, and sumoylatable p45/NF-E2. Chromatin immunoprecipitation assays further showed that the intact sumoylation site of p45/NF-E2 is required for its binding to the DNase I-hypersensitive sites of the β-globin locus control region. Finally, we demonstrated by stable transfection assay that only the wild-type p45, but not its mutant form p45 (K368R), could efficiently rescue β-globin gene expression in the p45-null, erythroid cell line CB3. These data together point to a model of mammalian β-like globin gene activation by sumoylated p45/NF-E2 in erythroid cells.

原文英語
頁(從 - 到)10365-10378
頁數14
期刊Molecular and Cellular Biology
25
發行號23
DOIs
出版狀態已發佈 - 十二月 2005
對外發佈Yes

    指紋

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

引用此

Shyu, Y. C., Lee, T. L., Ting, C. Y., Wen, S. C., Hsieh, L. J., Li, Y. C., Hwang, J. L., Lin, C. C., & Shen, C. K. J. (2005). Sumoylation of p45/NF-E2: Nuclear positioning and transcriptional activation of the mammalian β-like globin gene locus. Molecular and Cellular Biology, 25(23), 10365-10378. https://doi.org/10.1128/MCB.25.23.10365-10378.2005