Myeloid Expression of Cytochrome P450 4F3 Is Determined by a Lineage-specific Alternative Promoter

Peter Christmas, Nadia Carlesso, Haibo Shang, Shing Ming Cheng, Brittany M. Weber, Frederic I. Preffer, David T. Scadden, Roy J. Soberman

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The cytochrome P450 4F3 (CYP4F3) gene encodes two functionally distinct enzymes that differ only by the selection of exon 4 (CYP4F3A) or exon 3 (CYP4F3B). CYP4F3A inactivates leukotriene B4, a reaction that has significance for controlling inflammation. CYP4F3B converts arachidonic acid to 20-hydroxyeicosatetraenoic acid, a potent activator of protein kinase C. We have previously shown that mRNAs coding for CYP4F3A and CYP4F3B are generated from distinct transcription start sites in neutrophils and liver. We therefore investigated mechanisms that regulate the cell-specific expression of these two isoforms. Initially, we analyzed the distribution of CYP4F3 in human leukocytes and determined a lineage-specific pattern of isoform expression. CYP4F3A is expressed in myeloid cells and is coordinate with myeloid differentiation markers such as CD11b and myeloperoxidase during development in the bone marrow. In contrast, CYP4F3B expression is restricted to a small population of CD3+ T lymphocytes. We identified distinct transcriptional features in myeloid, lymphoid, and hepatic cells that indicate the presence of multiple promoters in the CYP4F3 gene. The hepatic promoter depends on a cluster of hepatocyte nuclear factor sites 123-155 bp upstream of the initiator ATG codon. The myeloid promoter spans 400 bp in a region 468-872 bp upstream of the ATG codon; it is associated with clusters of CACCT sites and can be activated by ZEB-2, a factor primarily characterized as a transcriptional repressor in cells that include lymphocytes. ZEB-2 interacts with C-terminal binding protein and Smads, and this would provide opportunities for integrating environmental signals in myelopoiesis and inflammation.

Original languageEnglish (US)
Pages (from-to)25133-25142
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number27
DOIs
StatePublished - Jul 4 2003
Externally publishedYes

Fingerprint

Cytochrome P-450 Enzyme System
Myeloid Cells
Exons
Protein Isoforms
Genes
Hepatocyte Nuclear Factors
Lymphocytes
Myelopoiesis
Inflammation
Leukotriene B4
T-cells
Initiator Codon
Transcription Initiation Site
Liver
Differentiation Antigens
Arachidonic Acid
Codon
Protein Kinase C
Peroxidase
Hepatocytes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Christmas, P., Carlesso, N., Shang, H., Cheng, S. M., Weber, B. M., Preffer, F. I., ... Soberman, R. J. (2003). Myeloid Expression of Cytochrome P450 4F3 Is Determined by a Lineage-specific Alternative Promoter. Journal of Biological Chemistry, 278(27), 25133-25142. https://doi.org/10.1074/jbc.M302106200

Myeloid Expression of Cytochrome P450 4F3 Is Determined by a Lineage-specific Alternative Promoter. / Christmas, Peter; Carlesso, Nadia; Shang, Haibo; Cheng, Shing Ming; Weber, Brittany M.; Preffer, Frederic I.; Scadden, David T.; Soberman, Roy J.

In: Journal of Biological Chemistry, Vol. 278, No. 27, 04.07.2003, p. 25133-25142.

Research output: Contribution to journalArticle

Christmas, P, Carlesso, N, Shang, H, Cheng, SM, Weber, BM, Preffer, FI, Scadden, DT & Soberman, RJ 2003, 'Myeloid Expression of Cytochrome P450 4F3 Is Determined by a Lineage-specific Alternative Promoter', Journal of Biological Chemistry, vol. 278, no. 27, pp. 25133-25142. https://doi.org/10.1074/jbc.M302106200
Christmas, Peter ; Carlesso, Nadia ; Shang, Haibo ; Cheng, Shing Ming ; Weber, Brittany M. ; Preffer, Frederic I. ; Scadden, David T. ; Soberman, Roy J. / Myeloid Expression of Cytochrome P450 4F3 Is Determined by a Lineage-specific Alternative Promoter. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 27. pp. 25133-25142.
@article{ca1841bd8a4e48d2b80a8a0cbbaaaa08,
title = "Myeloid Expression of Cytochrome P450 4F3 Is Determined by a Lineage-specific Alternative Promoter",
abstract = "The cytochrome P450 4F3 (CYP4F3) gene encodes two functionally distinct enzymes that differ only by the selection of exon 4 (CYP4F3A) or exon 3 (CYP4F3B). CYP4F3A inactivates leukotriene B4, a reaction that has significance for controlling inflammation. CYP4F3B converts arachidonic acid to 20-hydroxyeicosatetraenoic acid, a potent activator of protein kinase C. We have previously shown that mRNAs coding for CYP4F3A and CYP4F3B are generated from distinct transcription start sites in neutrophils and liver. We therefore investigated mechanisms that regulate the cell-specific expression of these two isoforms. Initially, we analyzed the distribution of CYP4F3 in human leukocytes and determined a lineage-specific pattern of isoform expression. CYP4F3A is expressed in myeloid cells and is coordinate with myeloid differentiation markers such as CD11b and myeloperoxidase during development in the bone marrow. In contrast, CYP4F3B expression is restricted to a small population of CD3+ T lymphocytes. We identified distinct transcriptional features in myeloid, lymphoid, and hepatic cells that indicate the presence of multiple promoters in the CYP4F3 gene. The hepatic promoter depends on a cluster of hepatocyte nuclear factor sites 123-155 bp upstream of the initiator ATG codon. The myeloid promoter spans 400 bp in a region 468-872 bp upstream of the ATG codon; it is associated with clusters of CACCT sites and can be activated by ZEB-2, a factor primarily characterized as a transcriptional repressor in cells that include lymphocytes. ZEB-2 interacts with C-terminal binding protein and Smads, and this would provide opportunities for integrating environmental signals in myelopoiesis and inflammation.",
author = "Peter Christmas and Nadia Carlesso and Haibo Shang and Cheng, {Shing Ming} and Weber, {Brittany M.} and Preffer, {Frederic I.} and Scadden, {David T.} and Soberman, {Roy J.}",
year = "2003",
month = "7",
day = "4",
doi = "10.1074/jbc.M302106200",
language = "English (US)",
volume = "278",
pages = "25133--25142",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "27",

}

TY - JOUR

T1 - Myeloid Expression of Cytochrome P450 4F3 Is Determined by a Lineage-specific Alternative Promoter

AU - Christmas, Peter

AU - Carlesso, Nadia

AU - Shang, Haibo

AU - Cheng, Shing Ming

AU - Weber, Brittany M.

AU - Preffer, Frederic I.

AU - Scadden, David T.

AU - Soberman, Roy J.

PY - 2003/7/4

Y1 - 2003/7/4

N2 - The cytochrome P450 4F3 (CYP4F3) gene encodes two functionally distinct enzymes that differ only by the selection of exon 4 (CYP4F3A) or exon 3 (CYP4F3B). CYP4F3A inactivates leukotriene B4, a reaction that has significance for controlling inflammation. CYP4F3B converts arachidonic acid to 20-hydroxyeicosatetraenoic acid, a potent activator of protein kinase C. We have previously shown that mRNAs coding for CYP4F3A and CYP4F3B are generated from distinct transcription start sites in neutrophils and liver. We therefore investigated mechanisms that regulate the cell-specific expression of these two isoforms. Initially, we analyzed the distribution of CYP4F3 in human leukocytes and determined a lineage-specific pattern of isoform expression. CYP4F3A is expressed in myeloid cells and is coordinate with myeloid differentiation markers such as CD11b and myeloperoxidase during development in the bone marrow. In contrast, CYP4F3B expression is restricted to a small population of CD3+ T lymphocytes. We identified distinct transcriptional features in myeloid, lymphoid, and hepatic cells that indicate the presence of multiple promoters in the CYP4F3 gene. The hepatic promoter depends on a cluster of hepatocyte nuclear factor sites 123-155 bp upstream of the initiator ATG codon. The myeloid promoter spans 400 bp in a region 468-872 bp upstream of the ATG codon; it is associated with clusters of CACCT sites and can be activated by ZEB-2, a factor primarily characterized as a transcriptional repressor in cells that include lymphocytes. ZEB-2 interacts with C-terminal binding protein and Smads, and this would provide opportunities for integrating environmental signals in myelopoiesis and inflammation.

AB - The cytochrome P450 4F3 (CYP4F3) gene encodes two functionally distinct enzymes that differ only by the selection of exon 4 (CYP4F3A) or exon 3 (CYP4F3B). CYP4F3A inactivates leukotriene B4, a reaction that has significance for controlling inflammation. CYP4F3B converts arachidonic acid to 20-hydroxyeicosatetraenoic acid, a potent activator of protein kinase C. We have previously shown that mRNAs coding for CYP4F3A and CYP4F3B are generated from distinct transcription start sites in neutrophils and liver. We therefore investigated mechanisms that regulate the cell-specific expression of these two isoforms. Initially, we analyzed the distribution of CYP4F3 in human leukocytes and determined a lineage-specific pattern of isoform expression. CYP4F3A is expressed in myeloid cells and is coordinate with myeloid differentiation markers such as CD11b and myeloperoxidase during development in the bone marrow. In contrast, CYP4F3B expression is restricted to a small population of CD3+ T lymphocytes. We identified distinct transcriptional features in myeloid, lymphoid, and hepatic cells that indicate the presence of multiple promoters in the CYP4F3 gene. The hepatic promoter depends on a cluster of hepatocyte nuclear factor sites 123-155 bp upstream of the initiator ATG codon. The myeloid promoter spans 400 bp in a region 468-872 bp upstream of the ATG codon; it is associated with clusters of CACCT sites and can be activated by ZEB-2, a factor primarily characterized as a transcriptional repressor in cells that include lymphocytes. ZEB-2 interacts with C-terminal binding protein and Smads, and this would provide opportunities for integrating environmental signals in myelopoiesis and inflammation.

UR - http://www.scopus.com/inward/record.url?scp=0041589346&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0041589346&partnerID=8YFLogxK

U2 - 10.1074/jbc.M302106200

DO - 10.1074/jbc.M302106200

M3 - Article

VL - 278

SP - 25133

EP - 25142

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 27

ER -