Article

Cell-cycle specific association of transcription factors and RNA polymerase II with the human β-globin gene locus†

  1. Michael Rosenberg‡,
  2. Alex Xiucheng Fan‡,
  3. I-Ju Lin,
  4. Shermi Y Liang,
  5. Jörg Bungert*

DOI: 10.1002/jcb.24542

Additional Information

Author Information

  1. Department of Biochemistry and Molecular Biology, Center for Epigenetics, Genetics Institute, Powell Gene Therapy Center, University of Florida, Gainesville, Florida

  1. ‡

    These authors should be considered co-first authors.

*Jörg Bungert, Ph.D., Department of Biochemistry, And Molecular Biology, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32610. Phone 352-273-8098, Email: jbungert@ufl.edu

  1. †

    This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: [10.1002/jcb.24542]

  2. ‡

    These authors should be considered co-first authors.

Publication History

  1. Accepted manuscript online: 20 MAR 2013 08:54AM EST
  2. Manuscript Accepted: 5 MAR 2013
  3. Manuscript Revised: 2 MAR 2013
  4. Manuscript Received: 11 MAY 2012

Funded by

  • NIH. Grant Number: RO1DK052356, R01DK052356S1, RO1DK083389

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

Get PDF (685K)

Keywords:

  • globin gene locus;
  • cell-cycle;
  • transcription factor;
  • mitosis;
  • RNA polymerase II

Abstract

The human β-globin genes are regulated by a locus control region (LCR) and are expressed at extremely high levels in erythroid cells. How transcriptional fidelity of highly expressed genes is regulated and maintained during the cell cycle is not completely understood. Here, we analyzed the association of transcription factor USF, the co-activator CBP, topoisomerase I (Topo I), basal transcription factor TFIIB, and RNA polymerase II (Pol II) with the β-globin gene locus at specific cell-cycle stages. The data demonstrate that while association of Pol II with globin locus associated chromatin decreased in mitotically arrested cells, it remained bound at lower levels at the γ-globin gene promoter. During early S-phase, association of CBP, USF and Pol II with the globin gene locus decreased. The reassociation of CBP and USF2 with the LCR preceded reassociation of Pol II, suggesting that these proteins together mediate recruitment of Pol II to the β-globin gene locus during S-phase. Finally, we analyzed the association of Topo I with the globin gene locus during late S-phase. In general, Topo I association correlated with the binding of Pol II. Inhibition of Topo I activity reduced Pol II binding at the LCR and intergenic regions but not at the γ-globin gene promoter. The data demonstrate dynamic associations of transcription factors with the globin gene locus during the cell cycle and support previous results showing that specific components of transcription complexes remain associated with highly transcribed genes during mitosis. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Get PDF (685K)