Faculty Collaboration Database

5'-flanking sequences mediate butyrate stimulation of embryonic globin gene expression in adult erythroid cells. Mol Cell Biol 1991 Sep;11(9):4690-7

Date

09/01/1991

Pubmed ID

1875947

Pubmed Central ID

PMC361361

DOI

10.1128/mcb.11.9.4690-4697.1991

Scopus ID

2-s2.0-0025912341 (requires institutional sign-in at Scopus site)   107 Citations

Abstract

A stable transfection assay was used to test the mechanism by which embryonic globin gene transcription is stimulated in adult erythroid cells exposed to butyric acid and its analogs. To test the appropriate expression and inducibility of chicken globin genes in murine erythroleukemia (MEL) cells, an adult chicken beta-globin gene construct was stably transfected. The chicken beta-globin gene was found to be coregulated with the endogenous adult mouse alpha-globin gene following induction of erythroid differentiation of the transfected MEL cells by incubation with either 2% dimethyl sulfoxide (DMSO) or 1 mM sodium butyrate (NaB). In contrast, a stably transfected embryonic chicken beta-type globin gene, rho, was downregulated during DMSO-induced MEL cell differentiation. However, incubation with NaB, which induces MEL cell differentiation, or alpha-amino butyrate, which does not induce differentiation of MEL cells, resulted in markedly increased levels of transcription from the stably transfected rho gene. Analysis of histone modification showed that induction of rho gene expression was not correlated with increased bulk histone acetylation. A region of 5'-flanking sequence extending from -569 to -725 bp upstream of the rho gene cap site was found to be required for both downregulation of rho gene expression during DMSO-induced differentiation and upregulation by treatment with NaB or alpha-amino butyrate. These data are support for a novel mechanism by which butyrate compounds can alter cellular gene expression through specific DNA sequences. The results reported here are also evidence that 5'-flanking sequences are involved in the suppression of embryonic globin gene expression in terminally differentiated adult erythroid cells.

Author List

Glauber JG, Wandersee NJ, Little JA, Ginder GD

MESH terms used to index this publication - Major topics in bold

Acetylation
Animals
Butyrates
Butyric Acid
Chick Embryo
DNA
Erythrocytes
Gene Expression Regulation
Globins
Histones
Leukemia, Erythroblastic, Acute
Mice
Ribonucleases
Transcription, Genetic
Tumor Cells, Cultured