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Volume 272, Number 32, Issue of August 8, 1997 pp. 20030-20037
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Globin Gene Silencing in Primary Erythroid Cultures
AN INHIBITORY ROLE FOR INTERLEUKIN-6

(Received for publication, May 16, 1997)

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

From the Departments of  Structural and Cellular Biology and ^§ Pediatrics, University of South Alabama, Mobile, Alabama 36688

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  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  and  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  gene silencing by interleukin-6. A potential interleukin-6 response element was identified in the  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.

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