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Article

A Positive Regulatory Feedback Loop between EKLF/KLF1 and TAL1/SCL Sustaining the Erythropoiesis

by
Chun-Hao Hung
1,2,†,
Tung-Liang Lee
1,†,
Anna Yu-Szu Huang
1,3,†,
Kang-Chung Yang
4,5,†,
Yu-Chiau Shyu
1,6,7,
Shau-Ching Wen
1,
Mu-Jie Lu
1,2,
Shinsheng Yuan
5,* and
Che-Kun James Shen
1,3,8,*
1
Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan
2
Department of Life Science, Institute of Genomic Research, National Yang-Ming University, Taipei 112, Taiwan
3
Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 10617, Taiwan
4
Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei 10617, Taiwan
5
Institute of Statistical Science, Academia Sinica, Taipei 11529, Taiwan
6
Community Medicine Research Center, Chang Gang Memorial Hospital, Keelung Branch, Keelung 204, Taiwan
7
Department of Nursing, Chang Gang University of Science and Technology, Taoyuan City 333, Taiwan
8
The PhD Program for Neural Regenerative Medicine, Taipei Medical University, Taipei 110, Taiwan
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2021, 22(15), 8024; https://doi.org/10.3390/ijms22158024
Submission received: 29 June 2021 / Revised: 23 July 2021 / Accepted: 25 July 2021 / Published: 27 July 2021
(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)
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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.
Keywords: erythroid differentiation; EKLF/KLF1; gene knockout; TAL1/SCL; global gene expression profiling; direct target genes; genomic footprinting of Tal1 promoter; transcriptional regulation erythroid differentiation; EKLF/KLF1; gene knockout; TAL1/SCL; global gene expression profiling; direct target genes; genomic footprinting of Tal1 promoter; transcriptional regulation

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MDPI and ACS Style

Hung, C.-H.; Lee, T.-L.; Huang, A.Y.-S.; Yang, K.-C.; Shyu, Y.-C.; Wen, S.-C.; Lu, M.-J.; Yuan, S.; Shen, C.-K.J. A Positive Regulatory Feedback Loop between EKLF/KLF1 and TAL1/SCL Sustaining the Erythropoiesis. Int. J. Mol. Sci. 2021, 22, 8024. https://doi.org/10.3390/ijms22158024

AMA Style

Hung C-H, Lee T-L, Huang AY-S, Yang K-C, Shyu Y-C, Wen S-C, Lu M-J, Yuan S, Shen C-KJ. A Positive Regulatory Feedback Loop between EKLF/KLF1 and TAL1/SCL Sustaining the Erythropoiesis. International Journal of Molecular Sciences. 2021; 22(15):8024. https://doi.org/10.3390/ijms22158024

Chicago/Turabian Style

Hung, Chun-Hao, Tung-Liang Lee, Anna Yu-Szu Huang, Kang-Chung Yang, Yu-Chiau Shyu, Shau-Ching Wen, Mu-Jie Lu, Shinsheng Yuan, and Che-Kun James Shen. 2021. "A Positive Regulatory Feedback Loop between EKLF/KLF1 and TAL1/SCL Sustaining the Erythropoiesis" International Journal of Molecular Sciences 22, no. 15: 8024. https://doi.org/10.3390/ijms22158024

APA Style

Hung, C.-H., Lee, T.-L., Huang, A. Y.-S., Yang, K.-C., Shyu, Y.-C., Wen, S.-C., Lu, M.-J., Yuan, S., & Shen, C.-K. J. (2021). A Positive Regulatory Feedback Loop between EKLF/KLF1 and TAL1/SCL Sustaining the Erythropoiesis. International Journal of Molecular Sciences, 22(15), 8024. https://doi.org/10.3390/ijms22158024

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