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p45 NF-E2 regulates expression of thromboxane synthase in megakaryocytes.

Publication ,  Journal Article
Deveaux, S; Cohen-Kaminsky, S; Shivdasani, RA; Andrews, NC; Filipe, A; Kuzniak, I; Orkin, SH; Roméo, PH; Mignotte, V
Published in: EMBO J
September 15, 1997

Transcription factor p45 NF-E2 is highly expressed in the erythroid and megakaryocytic lineages. Although p45 recognizes regulatory regions of several erythroid genes, mice deficient for this protein display only mild dyserythropoiesis but have abnormal megakaryocytes and lack circulating platelets. A number of megakaryocytic marker genes have been extensively studied, but none of them is regulated by NF-E2. To find target genes for p45 NF-E2 in megakaryopoiesis, we used an in vivo immunoselection assay: genomic fragments bound to p45 NF-E2 in the chromatin of a megakaryocytic cell line were immunoprecipitated with an anti-p45 antiserum and cloned. One of these fragments belongs to the second intron of the thromboxane synthase gene (TXS). We demonstrate that the TXS gene, which is mainly expressed in megakaryocytes, is indeed directly regulated by p45 NF-E2. First, its promoter contains a functional NF-E2 binding site; second, the intronic NF-E2 binding site is located within a chromatin-dependent enhancer element; third, p45-null murine megakaryocytes do not express detectable TXS mRNA, although TXS expression can be detected in other cells. These data, and the structure of the TXS promoter and enhancer, suggest that TXS belongs to a distinct subgroup of genes involved in platelet formation and function.

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Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

September 15, 1997

Volume

16

Issue

18

Start / End Page

5654 / 5661

Location

England

Related Subject Headings

  • Zinc Fingers
  • Transfection
  • Transcription Factors
  • Thromboxane-A Synthase
  • Regulatory Sequences, Nucleic Acid
  • Recombinant Proteins
  • Promoter Regions, Genetic
  • Polymerase Chain Reaction
  • NF-E2 Transcription Factor, p45 Subunit
  • NF-E2 Transcription Factor
 

Citation

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Deveaux, S., Cohen-Kaminsky, S., Shivdasani, R. A., Andrews, N. C., Filipe, A., Kuzniak, I., … Mignotte, V. (1997). p45 NF-E2 regulates expression of thromboxane synthase in megakaryocytes. EMBO J, 16(18), 5654–5661. https://doi.org/10.1093/emboj/16.18.5654
Deveaux, S., S. Cohen-Kaminsky, R. A. Shivdasani, N. C. Andrews, A. Filipe, I. Kuzniak, S. H. Orkin, P. H. Roméo, and V. Mignotte. “p45 NF-E2 regulates expression of thromboxane synthase in megakaryocytes.EMBO J 16, no. 18 (September 15, 1997): 5654–61. https://doi.org/10.1093/emboj/16.18.5654.
Deveaux S, Cohen-Kaminsky S, Shivdasani RA, Andrews NC, Filipe A, Kuzniak I, et al. p45 NF-E2 regulates expression of thromboxane synthase in megakaryocytes. EMBO J. 1997 Sep 15;16(18):5654–61.
Deveaux, S., et al. “p45 NF-E2 regulates expression of thromboxane synthase in megakaryocytes.EMBO J, vol. 16, no. 18, Sept. 1997, pp. 5654–61. Pubmed, doi:10.1093/emboj/16.18.5654.
Deveaux S, Cohen-Kaminsky S, Shivdasani RA, Andrews NC, Filipe A, Kuzniak I, Orkin SH, Roméo PH, Mignotte V. p45 NF-E2 regulates expression of thromboxane synthase in megakaryocytes. EMBO J. 1997 Sep 15;16(18):5654–5661.

Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

September 15, 1997

Volume

16

Issue

18

Start / End Page

5654 / 5661

Location

England

Related Subject Headings

  • Zinc Fingers
  • Transfection
  • Transcription Factors
  • Thromboxane-A Synthase
  • Regulatory Sequences, Nucleic Acid
  • Recombinant Proteins
  • Promoter Regions, Genetic
  • Polymerase Chain Reaction
  • NF-E2 Transcription Factor, p45 Subunit
  • NF-E2 Transcription Factor