Novel roles for KLF1 in erythropoiesis revealed by mRNA-seq

Genome Res. 2012 Dec;22(12):2385-98. doi: 10.1101/gr.135707.111. Epub 2012 Jul 26.


KLF1 (formerly known as EKLF) regulates the development of erythroid cells from bi-potent progenitor cells via the transcriptional activation of a diverse set of genes. Mice lacking Klf1 die in utero prior to E15 from severe anemia due to the inadequate expression of genes controlling hemoglobin production, cell membrane and cytoskeletal integrity, and the cell cycle. We have recently described the full repertoire of KLF1 binding sites in vivo by performing KLF1 ChIP-seq in primary erythroid tissue (E14.5 fetal liver). Here we describe the KLF1-dependent erythroid transcriptome by comparing mRNA-seq from Klf1(+/+) and Klf1(-/-) erythroid tissue. This has revealed novel target genes not previously obtainable by traditional microarray technology, and provided novel insights into the function of KLF1 as a transcriptional activator. We define a cis-regulatory module bound by KLF1, GATA1, TAL1, and EP300 that coordinates a core set of erythroid genes. We also describe a novel set of erythroid-specific promoters that drive high-level expression of otherwise ubiquitously expressed genes in erythroid cells. Our study has identified two novel lncRNAs that are dynamically expressed during erythroid differentiation, and discovered a role for KLF1 in directing apoptotic gene expression to drive the terminal stages of erythroid maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Blotting, Western
  • Cell Differentiation
  • Chromosome Mapping
  • E1A-Associated p300 Protein / genetics
  • E1A-Associated p300 Protein / metabolism
  • Erythroid Cells / cytology
  • Erythroid Cells / metabolism
  • Erythropoiesis / genetics*
  • GATA1 Transcription Factor / genetics
  • GATA1 Transcription Factor / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • In Situ Nick-End Labeling
  • Kruppel-Like Transcription Factors / genetics*
  • Kruppel-Like Transcription Factors / metabolism
  • Liver / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Sequence Analysis, RNA / methods
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Transcriptome*


  • Basic Helix-Loop-Helix Transcription Factors
  • GATA1 Transcription Factor
  • Gata1 protein, mouse
  • Kruppel-Like Transcription Factors
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Tal1 protein, mouse
  • erythroid Kruppel-like factor
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse