Transcriptional and posttranscriptional modulation of human neutrophil elastase gene expression

Kunihiko Yoshimura, Ronald Crystal

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Human neutrophil elastase (NE), a 29-Kd potent serine protease stored in azurophilic granules of mature neutrophils, is coded for by the NE gene, a single copy gene with 5 exons spanning a 6-kb segment of chromosome 11 at q14. With the knowledge that the NE gene expression is limited to early myeloid cell differentiation, mechanisms modulating expression of the NE gene were evaluated in the HL-60 promyelocytic leukemia cell line, a model of early bone marrow precursor cells. Consistent with the presence of NE messenger RNA (mRNA) transcripts in undifferentiated HL-60 cells, nuclear transcription run-on analyses showed that HL-60 cells actively transcribed the NE gene. However, the transcription rate of the NE gene was relatively low, only 40% of the myeloperoxidase gene, a gene expressed in parallel with NE. When induced toward the mononuclear phagocytic lineage with phorbol 12-myristate 13-acetate (PMA), HL-60 cells exhibited marked suppression of NE gene transcription, declining to 17% of the resting rate within 2 days. Induction toward mononuclear phagocytic lineage differentiation caused no change in NE mRNA transcript half-life (T1/2), but mRNA levels decreased markedly over time, with levels undetectable 1.5 days after PMA stimulation. In contrast, when induced toward the myelocytic lineage with dimethyl sulfoxide, the rate of NE gene transcription increased 1.9-fold within 5 days. Interestingly, the mRNA transcript levels increased 2.5-fold by 5 days despite the fact that induction toward myelocytic lineage differentiation was accompanied by a marked reduction of NE mRNA transcript T1/2. Together, these observations suggest that the NE gene expression during bone marrow differentiation is modulated mainly at the transcriptional level, with some posttranscriptional modulation contributing, particularly during myelocytic lineage differentiation. This is a US government work. There are no restrictions on its use.

Original languageEnglish
Pages (from-to)2733-2740
Number of pages8
JournalBlood
Volume79
Issue number10
Publication statusPublished - 15 May 1992
Externally publishedYes

Fingerprint

Leukocyte Elastase
Gene expression
Modulation
Gene Expression
Genes
Transcription
HL-60 Cells
Messenger RNA
Bone
Acetates
Chromosomes, Human, Pair 11
Serine Proteases
Myeloid Cells
Chromosomes
Dimethyl Sulfoxide
Bone Marrow Cells
Peroxidase
Half-Life
Cell Differentiation
Exons

ASJC Scopus subject areas

  • Hematology

Cite this

Transcriptional and posttranscriptional modulation of human neutrophil elastase gene expression. / Yoshimura, Kunihiko; Crystal, Ronald.

In: Blood, Vol. 79, No. 10, 15.05.1992, p. 2733-2740.

Research output: Contribution to journalArticle

@article{4d1cd0811d7645f78e47421dfd51b068,
title = "Transcriptional and posttranscriptional modulation of human neutrophil elastase gene expression",
abstract = "Human neutrophil elastase (NE), a 29-Kd potent serine protease stored in azurophilic granules of mature neutrophils, is coded for by the NE gene, a single copy gene with 5 exons spanning a 6-kb segment of chromosome 11 at q14. With the knowledge that the NE gene expression is limited to early myeloid cell differentiation, mechanisms modulating expression of the NE gene were evaluated in the HL-60 promyelocytic leukemia cell line, a model of early bone marrow precursor cells. Consistent with the presence of NE messenger RNA (mRNA) transcripts in undifferentiated HL-60 cells, nuclear transcription run-on analyses showed that HL-60 cells actively transcribed the NE gene. However, the transcription rate of the NE gene was relatively low, only 40{\%} of the myeloperoxidase gene, a gene expressed in parallel with NE. When induced toward the mononuclear phagocytic lineage with phorbol 12-myristate 13-acetate (PMA), HL-60 cells exhibited marked suppression of NE gene transcription, declining to 17{\%} of the resting rate within 2 days. Induction toward mononuclear phagocytic lineage differentiation caused no change in NE mRNA transcript half-life (T1/2), but mRNA levels decreased markedly over time, with levels undetectable 1.5 days after PMA stimulation. In contrast, when induced toward the myelocytic lineage with dimethyl sulfoxide, the rate of NE gene transcription increased 1.9-fold within 5 days. Interestingly, the mRNA transcript levels increased 2.5-fold by 5 days despite the fact that induction toward myelocytic lineage differentiation was accompanied by a marked reduction of NE mRNA transcript T1/2. Together, these observations suggest that the NE gene expression during bone marrow differentiation is modulated mainly at the transcriptional level, with some posttranscriptional modulation contributing, particularly during myelocytic lineage differentiation. This is a US government work. There are no restrictions on its use.",
author = "Kunihiko Yoshimura and Ronald Crystal",
year = "1992",
month = "5",
day = "15",
language = "English",
volume = "79",
pages = "2733--2740",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "10",

}

TY - JOUR

T1 - Transcriptional and posttranscriptional modulation of human neutrophil elastase gene expression

AU - Yoshimura, Kunihiko

AU - Crystal, Ronald

PY - 1992/5/15

Y1 - 1992/5/15

N2 - Human neutrophil elastase (NE), a 29-Kd potent serine protease stored in azurophilic granules of mature neutrophils, is coded for by the NE gene, a single copy gene with 5 exons spanning a 6-kb segment of chromosome 11 at q14. With the knowledge that the NE gene expression is limited to early myeloid cell differentiation, mechanisms modulating expression of the NE gene were evaluated in the HL-60 promyelocytic leukemia cell line, a model of early bone marrow precursor cells. Consistent with the presence of NE messenger RNA (mRNA) transcripts in undifferentiated HL-60 cells, nuclear transcription run-on analyses showed that HL-60 cells actively transcribed the NE gene. However, the transcription rate of the NE gene was relatively low, only 40% of the myeloperoxidase gene, a gene expressed in parallel with NE. When induced toward the mononuclear phagocytic lineage with phorbol 12-myristate 13-acetate (PMA), HL-60 cells exhibited marked suppression of NE gene transcription, declining to 17% of the resting rate within 2 days. Induction toward mononuclear phagocytic lineage differentiation caused no change in NE mRNA transcript half-life (T1/2), but mRNA levels decreased markedly over time, with levels undetectable 1.5 days after PMA stimulation. In contrast, when induced toward the myelocytic lineage with dimethyl sulfoxide, the rate of NE gene transcription increased 1.9-fold within 5 days. Interestingly, the mRNA transcript levels increased 2.5-fold by 5 days despite the fact that induction toward myelocytic lineage differentiation was accompanied by a marked reduction of NE mRNA transcript T1/2. Together, these observations suggest that the NE gene expression during bone marrow differentiation is modulated mainly at the transcriptional level, with some posttranscriptional modulation contributing, particularly during myelocytic lineage differentiation. This is a US government work. There are no restrictions on its use.

AB - Human neutrophil elastase (NE), a 29-Kd potent serine protease stored in azurophilic granules of mature neutrophils, is coded for by the NE gene, a single copy gene with 5 exons spanning a 6-kb segment of chromosome 11 at q14. With the knowledge that the NE gene expression is limited to early myeloid cell differentiation, mechanisms modulating expression of the NE gene were evaluated in the HL-60 promyelocytic leukemia cell line, a model of early bone marrow precursor cells. Consistent with the presence of NE messenger RNA (mRNA) transcripts in undifferentiated HL-60 cells, nuclear transcription run-on analyses showed that HL-60 cells actively transcribed the NE gene. However, the transcription rate of the NE gene was relatively low, only 40% of the myeloperoxidase gene, a gene expressed in parallel with NE. When induced toward the mononuclear phagocytic lineage with phorbol 12-myristate 13-acetate (PMA), HL-60 cells exhibited marked suppression of NE gene transcription, declining to 17% of the resting rate within 2 days. Induction toward mononuclear phagocytic lineage differentiation caused no change in NE mRNA transcript half-life (T1/2), but mRNA levels decreased markedly over time, with levels undetectable 1.5 days after PMA stimulation. In contrast, when induced toward the myelocytic lineage with dimethyl sulfoxide, the rate of NE gene transcription increased 1.9-fold within 5 days. Interestingly, the mRNA transcript levels increased 2.5-fold by 5 days despite the fact that induction toward myelocytic lineage differentiation was accompanied by a marked reduction of NE mRNA transcript T1/2. Together, these observations suggest that the NE gene expression during bone marrow differentiation is modulated mainly at the transcriptional level, with some posttranscriptional modulation contributing, particularly during myelocytic lineage differentiation. This is a US government work. There are no restrictions on its use.

UR - http://www.scopus.com/inward/record.url?scp=0026697026&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026697026&partnerID=8YFLogxK

M3 - Article

C2 - 1586720

AN - SCOPUS:0026697026

VL - 79

SP - 2733

EP - 2740

JO - Blood

JF - Blood

SN - 0006-4971

IS - 10

ER -