Globin gene silencing in primary erythroid cultures. An inhibitory role for interleukin-6

Amy E. Ferry, Surendra B. Baliga, Carlos Monteiro, Betty S. Pace

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

There are numerous similarities between the erythroid and megakaryocytic lineages which suggest that commitment to either lineage occurs relatively late in hematopoiesis. Commitment toward megakaryocyte development requires obligatory silencing of erythroid-specific genes. Therefore, we investigated the effects of interleukin-6, a known inducer of thrombocyte production, on globin gene expression during erythroid differentiation. Studies in K562 cells demonstrated inhibition of γ globin gene mRNA production and chain biosynthesis in the presence of exogenous interleukin-6 which was abrogated by anti-interleukin-6 monoclonal antibody. Similar studies in primary erythroid progenitors showed inhibition of burst-forming unit-erythroid colony formation when interleukin-6 was added late in cultures with decreased γ and β globin gene mRNA production. Protein binding studies demonstrated an increase in activator protein-1 binding to its consensus sequence by 24 h of interleukin-6 treatment. Inhibition of activator protein-1 gene activity had no effect on γ gene silencing by interleukin-6. A potential interleukin- 6 response element was identified in the γ globin gene. Interleukin-6 treatment led to a rapid increase in protein binding to the target DNA sequence. These results suggest that interleukin-6 may play an important role in globin gene silencing during megakaryocytic lineage commitment.

Original languageEnglish (US)
Pages (from-to)20030-20037
Number of pages8
JournalJournal of Biological Chemistry
Volume272
Issue number32
DOIs
StatePublished - Aug 8 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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