Transcriptional and posttranscriptional modulation of human neutrophil elastase gene expression. Academic Article uri icon

Overview

MeSH

  • Blotting, Northern
  • Cell Differentiation
  • Cell Line
  • Chromosomes, Human, Pair 11
  • Dimethyl Sulfoxide
  • Exons
  • Genes
  • HeLa Cells
  • Humans
  • Kinetics
  • Leukocyte Elastase
  • Monocytes
  • RNA, Messenger
  • T-Lymphocytes
  • Tetradecanoylphorbol Acetate
  • Time Factors

MeSH Major

  • Gene Expression Regulation, Enzymologic
  • Pancreatic Elastase
  • RNA Processing, Post-Transcriptional
  • Transcription, Genetic

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.

publication date

  • May 15, 1992

has subject area

  • Blotting, Northern
  • Cell Differentiation
  • Cell Line
  • Chromosomes, Human, Pair 11
  • Dimethyl Sulfoxide
  • Exons
  • Gene Expression Regulation, Enzymologic
  • Genes
  • HeLa Cells
  • Humans
  • Kinetics
  • Leukocyte Elastase
  • Monocytes
  • Pancreatic Elastase
  • RNA Processing, Post-Transcriptional
  • RNA, Messenger
  • T-Lymphocytes
  • Tetradecanoylphorbol Acetate
  • Time Factors
  • Transcription, Genetic

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 1586720

Additional Document Info

start page

  • 2733

end page

  • 2740

volume

  • 79

number

  • 10