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PMID: 6222378 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Hexamethylenebisacetamide-resistant murine erythroleukemia cells have altered patterns of inducer-mediated chromatin changes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 80 ·No. 11 ·1983-06-00 ·Pages 3349-53

Sheffery M, Rifkind RA, Marks PA

Abstract

We determined inducer-mediated changes in chromatin structure near the globin genes in a variant line of murine erythroleukemia cells (MELC). The variant cell line, R1, was derived from the inducer-sensitive DS19 cell line by selection for inducer-resistance. R1 cells are resistant to induction of erythroid differentiation by hexamethylenebisacetamide (HMBA) whereas the parental line is HMBA-sensitive. Uninduced MELC (both inducer-sensitive DS19 cells and inducer-resistant R1 cells) have DNase I-sensitive sites in chromatin containing the alpha 1- and beta maj-globin genes. These nuclease-sensitive regions are located within the beta maj-globin second intervening sequence (IVS2) and near the alpha 1-globin gene 5' cap site. Culture with HMBA causes changes in chromatin structure in both parental and variant cell lines. In DS19 cells, the DNase I-sensitive site within the beta maj-globin IVS2 becomes more resistant to nuclease cleavage, and a new DNase I-sensitive region develops near the beta maj-globin cap site. In addition, the nuclease-sensitive region adjacent to the cap site of the alpha 1-globin gene increases, and a novel 5' nuclease-sensitive site is also established. In R1 cells, HMBA-mediated changes in chromatin structure are incomplete. The DNase I-sensitive site within the beta maj-globin IVS2 becomes more resistant to nuclease cleavage, but the nuclease sensitivity near the beta maj-globin cap site does not increase to the extent observed in DS19 cells. The pattern of nuclease sensitivity near the alpha 1-globin gene is essentially unchanged after culture of R1 cells with HMBA. Thus, in R1 cells, resistance to HMBA-induced expression of globin genes is associated with failure to detect inducer-mediated changes in chromatin structure 5' to the cap site of the alpha 1- and beta maj-globin genes. These results also suggest that the increased nuclease resistance of a site in the beta maj-globin IVS2 does not depend on the establishment of a DNase I-sensitive region near the beta maj-globin gene cap site.

MeSH Terms
Acetamides/pharmacology Animals Cell Line Chromatin/drug effects,physiology Deoxyribonuclease I Drug Resistance Endodeoxyribonucleases Genetic Variation Leukemia, Experimental/genetics,physiopathology Mice
Chemicals
Acetamides Chromatin Endodeoxyribonucleases Deoxyribonuclease I hexamethylene bisacetamide
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sheffery M
Rifkind R A
Marks P A
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38 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
DOI
10.1073/pnas.80.11.3349
Published
1983-06-00
Pages
3349-53
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC394040
Subset
IM
Grants
NCI NIH HHS · CA-08748 · United States
NCI NIH HHS · P01 CA-31768 · United States
External Links
PubMed source DOI: 10.1073/pnas.80.11.3349 PMC Full Text View journal details
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