Sequential activation of genes for heme pathway enzymes during erythroid differentiation of mouse Friend virus-transformed erythroleukemia cells

Hiroyoshi Fujita, Masayuki Yamamoto, Takashi Yamagami, Norio Hayashi, Terry R. Bishop, Hubert De Verneuil, Takeo Yoshinaga, Shigeki Shibahara, Richard Morimoto, Shigeru Sassa

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

Changes in the level of transcripts encoding enzymes of the heme biosynthetic pathway as well as those encoding ubiquitous proteins were examined in murine Friend virus-transformed erythroleukemia cells during erythroid cell differentiation induced by chemicals including dimethyl sulfoxide (DMSO). Early changes following DMSO treatment were marked decreases in mRNAs for three ubiquitous proteins, i.e., a 70 kDa heat shock protein (< 6 h), heme oxygenase and nonspecific δ-aminolevulinate synthase (ALAS) (< 12 h). These changes were followed by sequential increases in mRNAs for enzymes in the heme biosynthetic pathway. Namely, mRNAs for the erythroid-specific ALAS, δ-aminolevulinate dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase started to increase at 12, 18, 18-24 and 24 h, respectively. Nuclear runoff studies revealed that these changes are largely transcriptional. Treatments with other inducers or erythroid differentiation, e.g., hexamethylene bisacetamide, n-butyric acid and N′-methylnicotinamide, also showed similar effects on mRNAs as those following DMSO. These findings suggest that both suppression of ubiquitous genes and activation of heme pathway enzyme genes are associated with erythroid differentiation, and the former occurs preceding changes in the latter.

Original languageEnglish
Pages (from-to)311-316
Number of pages6
JournalBBA - Gene Structure and Expression
Volume1090
Issue number3
DOIs
Publication statusPublished - 1991 Nov 11

Keywords

  • Erythroleukemia cell
  • Heme oxygenase
  • Heme synthesis
  • Sequential activation
  • δ-Aminolevulinate synthase

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Genetics

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