Defective erythropoiesis in transgenic mice expressing dominant-negative upstream stimulatory factor

Shermi Y. Liang, Babak Moghimi, Valerie J. Crusselle-Davis, I. Ju Lin, Michael H. Rosenberg, Xingguo Li, John Strouboulis, Suming Huang, Jörg Bungert

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13 Scopus citations

Abstract

Transcription factor USF is a ubiquitously expressed member of the helix-loop-helix family of proteins. It binds with high affinity to E-box elements and, through interaction with coactivators, aids in the formation of transcription complexes. Previous work demonstrated that USF regulates genes during erythroid differentiation, including HoxB4 and β-globin. Here, we show that the erythroid cell-specific expression of a dominant-negative mutant of USF, A-USF, in transgenic mice reduces the expression of all β-type globin genes and leads to the diminished association of RNA polymerase II with locus control region element HS2 and with the β-globin gene promoter. We further show that the expression of A-USF reduces the expression of several key erythroid cell-specific transcription factors, including EKLF and Tal-1. We provide evidence demonstrating that USF interacts with known regulatory DNA elements in the EKLF and Tal-1 gene loci in erythroid cells. Furthermore, A-USF-expressing transgenic mice exhibit a defect in the formation of CD71 + progenitor and Ter-119+ mature erythroid cells. In summary, the data demonstrate that USF regulates globin gene expression indirectly by enhancing the expression of erythroid transcription factors and directly by mediating the recruitment of transcription complexes to the globin gene locus.

Original languageEnglish (US)
Pages (from-to)5900-5910
Number of pages11
JournalMolecular and cellular biology
Volume29
Issue number21
DOIs
StatePublished - Nov 2009

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Liang, S. Y., Moghimi, B., Crusselle-Davis, V. J., Lin, I. J., Rosenberg, M. H., Li, X., Strouboulis, J., Huang, S., & Bungert, J. (2009). Defective erythropoiesis in transgenic mice expressing dominant-negative upstream stimulatory factor. Molecular and cellular biology, 29(21), 5900-5910. https://doi.org/10.1128/MCB.00419-09