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PMID: 6204332 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Activation of a chicken embryonic globin gene in adult erythroid cells by 5-azacytidine and sodium butyrate.

Ginder GD, Whitters MJ, Pohlman JK

Abstract

Adult White Leghorn chickens were rendered anemic by injection with 1-acetyl-2-phenylhydrazine and then treated with parenteral 5-azacytidine, and levels of embryonic globin RNA in circulating reticulocytes were measured. A very small but detectable amount of correctly initiated embryonic p-type globin RNA was detected in reticulocytes from birds treated with 5-azacytidine, while none was detected in reticulocytes from those receiving only phenylhydrazine or phenylhydrazine plus 1-beta-D-arabinofuranosylcytosine (cytosine arabinonucleoside). An attempt to increase embryonic globin RNA induction by treatment with parenteral sodium butyrate after 7 days of 5-azacytidine administration resulted in a 5- to 10-fold increase in the level of embryonic globin RNA. However, sodium butyrate did not induce embryonic gene expression when given alone or after treatment with cytosine arabinonucleoside. Sodium butyrate treatment also caused a DNase I-hypersensitive site to be exposed at the 5' end of the rho-globin gene only after 5-azacytidine induced demethylation of several CpG sites in and around the gene. The implications of this model of gene activation in vivo are discussed in the context of multistep gene regulation.

MeSH Terms
Animals Azacitidine/pharmacology Base Sequence Butyrates/pharmacology Butyric Acid Chick Embryo Chickens DNA/isolation & purification DNA Restriction Enzymes Genes/drug effects Globins/biosynthesis,genetics Nucleic Acid Hybridization Reticulocytes/metabolism
Chemicals
Butyrates Butyric Acid Globins DNA DNA Restriction Enzymes Azacitidine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ginder G D
Whitters M J
Pohlman J K
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41 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1984-07-00
Pages
3954-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC345346
Subset
IM
Grants
NIADDK NIH HHS · AM 29902 · United States
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