A positive regulatory feedback loop between eklf/klf1 and tal1/scl sustaining the erythropoiesis

Chun Hao Hung, Tung Liang Lee, Anna Yu Szu Huang, Kang Chung Yang, Yu Chiau Shyu, Hau Ching Wen, Mu Jie Lu, Shinsheng Yuan, Che Kun James Shen

Research output: Contribution to journalArticlepeer-review

Abstract

The erythroid Krüppel-like factor EKLF/KLF1 is a hematopoietic transcription factor binding to the CACCC DNA motif and participating in the regulation of erythroid differentiation. With combined use of microarray-based gene expression profiling and the promoter-based ChIP-chip assay of E14.5 fetal liver cells from wild type (WT) and EKLF-knockout (Eklf−/−) mouse embryos, we identified the pathways and direct target genes activated or repressed by EKLF. This genome-wide study together with the molecular/cellular analysis of the mouse erythroleukemic cells (MEL) indicate that among the downstream direct target genes of EKLF is Tal1/Scl. Tal1/Scl encodes another DNA-binding hematopoietic transcription factor TAL1/SCL, known to be an Eklf activator and essential for definitive erythroid differentiation. Further identification of the authentic Tal gene promoter in combination with the in vivo genomic footprinting approach and DNA reporter assay demonstrate that EKLF activates the Tal gene through binding to a specific CACCC motif located in its promoter. These data establish the existence of a previously unknow positive regulatory feedback loop between two DNA-binding hematopoietic transcription factors, which sustains mammalian erythropoiesis.

Original languageEnglish
Article number8024
JournalInternational journal of molecular sciences
Volume22
Issue number15
DOIs
Publication statusPublished - Aug 2021

Keywords

  • Direct target genes
  • EKLF/ KLF1
  • Erythroid differentiation
  • Gene knockout
  • Genomic footprinting of Tal1 promoter
  • Global gene expression profiling
  • TAL1/ SCL
  • Transcriptional regulation

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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