Gene expression during terminal differentiation: Dexamethasone suppression of inducer-mediated α(1)- and β(maj)-globin gene expression Journal Article
| Authors: | Kaneda, T.; Murate, T.; Sheffery, M.; Brown, K.; Rifkind, R. A.; Marks, P. A. |
| Article Title: | Gene expression during terminal differentiation: Dexamethasone suppression of inducer-mediated α(1)- and β(maj)-globin gene expression |
| Abstract: | Previous studies demonstrated that hexamethylenebisacetamide (HMBA)-mediated murine erythroleukemia cell (MELC) commitment to terminal division could be supressed by dexamethasone. A rapid (<2 hr) increase (step-up) in commitment to terminal cell division was observed if, after 60-70 hr in culture with inducer and steroid, MELC were transferred to medium with HMBA alone. This step-up commitment was not inhibited by actinomycin or cordycepin but was blocked by cycloheximide. In this study, we show that dexamethasone blocks HMBA-mediated activation of α1- β(maj)-globin gene transcription but not the induced chromatin change characterized by appearance of DNase I-hypersensitive regions upstream from the 5' cap sites of the α1 and β(maj)-globin genes. A rapid (<2 hr) activation (step-up) of α1-globin gene transcription was observed if, after 48-60 hr in culture with HMBA and dexamethasone, MELC were transferred to medium with HMBA alone. Activation of transcription of the β(maj)-globin gene requires 12-24 hr of further culture. Cycloheximide inhibits step-up transcription of both globin genes. Thus, dexamethasone blocks HMBA-mediated modulation of transcription of several nonlinked genes whose expression is altered in a coordinated manner during induced MELC terminal differentiation. Further, the steroid blocks at a late step, a step after that which is rate-limiting to HMBA-mediated MELC differentiation. |
| Keywords: | nonhuman; animals; mice; cell division; heredity; gene expression; cell line; dexamethasone; cell differentiation; transcription, genetic; in vitro study; gene expression regulation; drug antagonism; cell culture; chromatin; murinae; dactinomycin; radioisotope; globins; beta globin; leukemia, erythroblastic, acute; cycloheximide; drug comparison; alpha globin; hexamethylenebisacetamide; acetamides; priority journal; cordycepin; blood and hemopoietic system |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 82 |
| Issue: | 15 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1985-08-01 |
| Start Page: | 5020 |
| End Page: | 5024 |
| Language: | English |
| DOI: | 10.1073/pnas.82.15.5020 |
| PROVIDER: | scopus |
| PMCID: | PMC390490 |
| PUBMED: | 3860841 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 26 October 2021 -- Source: Scopus |
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