Regulation of the PU.1 gene by distal elements

Youlin Li, Yutaka Okuno, Pu Zhang, Hanna S. Radomska, Hui Min Chen, Hiromi Iwasaki, Koichi Akashi, Michael J. Klemsz, Scott R. McKercher, Richard A. Maki, Daniel G. Tenen

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

The transcription factor PU.1 (also known as Spi-1) plays a critical role in the development of the myeloid lineages, and myeloid cells derived from PU.1-/- animals are blocked at the earliest stage of myeloid differentiation. Expression of the PU.1 gene is tightly regulated during normal hematopoietic development, and dysregulation of PU.1 expression can lead to erythroleukemia. However, relatively little is known about how the PU.1 gene is regulated in vivo. Here it is shown that myeloid cell type-specific expression of PU.1 in stable cell lines and transgenic animals is conferred by a 91-kilobase (kb) murine genomic DNA fragment that consists of the entire PU.1 gene (20 kb) plus approximately 35 kb of upstream and downstream sequences, respectively. To further map the important transcriptional regulatory elements, deoxyribonuclease I hypersensitive site mapping studies revealed at least 3 clusters in the PU.1 gene. A 3.5-kb fragment containing one of these deoxyribonuclease I hypersensitive sites, located -14 kb 5′ of the transcriptional start site, conferred myeloid cell type-specific expression in stably transfected cell lines, suggesting that within this region is an element important for myeloid specific expression of PU.1. Further analysis of this myeloid-specific regulatory element will provide insight into the regulation of this key transcriptional regulator and may be useful as a tool for targeting expression to the myeloid lineage.

Original languageEnglish
Pages (from-to)2958-2965
Number of pages8
JournalBlood
Volume98
Issue number10
DOIs
Publication statusPublished - Nov 15 2001

Fingerprint

Myeloid Cells
Genes
Deoxyribonuclease I
Animals
Transcriptional Regulatory Elements
Cells
Cell Line
Leukemia, Erythroblastic, Acute
Genetically Modified Animals
DNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Li, Y., Okuno, Y., Zhang, P., Radomska, H. S., Chen, H. M., Iwasaki, H., ... Tenen, D. G. (2001). Regulation of the PU.1 gene by distal elements. Blood, 98(10), 2958-2965. https://doi.org/10.1182/blood.V98.10.2958

Regulation of the PU.1 gene by distal elements. / Li, Youlin; Okuno, Yutaka; Zhang, Pu; Radomska, Hanna S.; Chen, Hui Min; Iwasaki, Hiromi; Akashi, Koichi; Klemsz, Michael J.; McKercher, Scott R.; Maki, Richard A.; Tenen, Daniel G.

In: Blood, Vol. 98, No. 10, 15.11.2001, p. 2958-2965.

Research output: Contribution to journalArticle

Li, Y, Okuno, Y, Zhang, P, Radomska, HS, Chen, HM, Iwasaki, H, Akashi, K, Klemsz, MJ, McKercher, SR, Maki, RA & Tenen, DG 2001, 'Regulation of the PU.1 gene by distal elements', Blood, vol. 98, no. 10, pp. 2958-2965. https://doi.org/10.1182/blood.V98.10.2958
Li Y, Okuno Y, Zhang P, Radomska HS, Chen HM, Iwasaki H et al. Regulation of the PU.1 gene by distal elements. Blood. 2001 Nov 15;98(10):2958-2965. https://doi.org/10.1182/blood.V98.10.2958
Li, Youlin ; Okuno, Yutaka ; Zhang, Pu ; Radomska, Hanna S. ; Chen, Hui Min ; Iwasaki, Hiromi ; Akashi, Koichi ; Klemsz, Michael J. ; McKercher, Scott R. ; Maki, Richard A. ; Tenen, Daniel G. / Regulation of the PU.1 gene by distal elements. In: Blood. 2001 ; Vol. 98, No. 10. pp. 2958-2965.
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