A global role for KLF1 in erythropoiesis revealed by ChIP-seq in primary erythroid cells
- Michael R Tallack1,
- Tom Whitington1,
- Wai Shan Yuen1,
- Elanor N Wainwright1,
- Janelle R Keys1,
- Brooke B Gardiner2,
- Ehsan Nourbakhsh3,
- Nicole Cloonan2,
- Sean M Grimmond3,
- Timothy L Bailey1 and
- Andrew C Perkins4,5
- 1 Institute for Molecular Bioscience, The University of Queensland;
- 2 Queensland Centre for Medical Genomics, Institute for Molecular Bioscience;
- 3 Queenland Centre for Medical Genomics, Institute for Molecular Bioscience;
- 4 Institute for Molecular Bioscience; The University of Queensland; Brisbane, Queensland, 4072; Austra
- * Corresponding author; email: a.perkins{at}imb.uq.edu.au
Abstract
KLF1 (EKLF) regulates a diverse suite of genes to direct erythroid cell differentiation from bi-potent 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 beta-globin, 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, co-ordination 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 co-operation with other transcription factors, in particular the erythroid transcription factor GATA1, to maintain homeostasis in the erythroid compartment.
Footnotes
- Received February 11, 2010.
- Accepted April 29, 2010.
- Copyright © 2010, Cold Spring Harbor Laboratory Press
