A global role for KLF1 in erythropoiesis revealed by ChIP-seq in primary erythroid cells

  1. Andrew C. Perkins1,3,5
  1. 1 Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia;
  2. 2 Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia;
  3. 3 The Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia
    1. 4 These authors contributed equally to this work.

    Abstract

    KLF1 regulates a diverse suite of genes to direct erythroid cell differentiation from bipotent progenitors. To determine the local cis-regulatory contexts and transcription factor networks in which KLF1 operates, we performed KLF1 ChIP-seq in the mouse. We found at least 945 sites in the genome of E14.5 fetal liver erythroid cells which are occupied by endogenous KLF1. Many of these recovered sites reside in erythroid gene promoters such as Hbb-b1, but the majority are distant to any known gene. Our data suggests KLF1 directly regulates most aspects of terminal erythroid differentiation including production of alpha- and beta-globin protein chains, heme biosynthesis, coordination of proliferation and anti-apoptotic pathways, and construction of the red cell membrane and cytoskeleton by functioning primarily as a transcriptional activator. Additionally, we suggest new mechanisms for KLF1 cooperation with other transcription factors, in particular the erythroid transcription factor GATA1, to maintain homeostasis in the erythroid compartment.

    Footnotes

    • 5 Corresponding authors.

      E-mail s.grimmond{at}imb.uq.edu.au; fax 617-3346-2101.

      E-mail t.bailey{at}imb.uq.edu.au; fax 617-3346-2101.

      E-mail a.perkins{at}imb.uq.edu.au; fax 617-3346-2101.

    • [Supplemental material is available online at http://www.genome.org. The sequence data from this study have been submitted to NCBI Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo) under accession no. GSE20478.]

    • Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.106575.110.

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