title: Sequential activation of genes for heme pathway enzymes during erythroid differentiation of mouse Friend virus-transformed erythroleukemia cells.
abstract: Changes in the level of transcripts encoding enzymes of the heme biosynthetic pathway as well as those encoding ubiquitous proteins were examined in murine Friend virus-transformed erythroleukemia cells during erythroid cell differentiation induced by chemicals including dimethyl sulfoxide (DMSO). Early changes following DMSO treatment were marked decreases in mRNAs for three ubiquitous proteins, i.e., a 70 kDa heat shock protein (less than 6 h), heme oxygenase and nonspecific delta-aminolevulinate synthase (ALAS) (less than 12 h). These changes were followed by sequential increases in mRNAs for enzymes in the heme biosynthetic pathway. Namely, mRNAs for the erythroid-specific ALAS, delta-aminolevulinate dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase started to increase at 12, 18, 18-24 and 24 h, respectively. Nuclear runoff studies revealed that these changes are largely transcriptional. Treatments with other inducers of erythroid differentiation, e.g., hexamethylene bisacetamide, n-butyric acid and N'-methylnicotinamide, also showed similar effects on mRNAs as those following DMSO. These findings suggest that both suppression of ubiquitous genes and activation of heme pathway enzyme genes are associated with erythroid differentiation, and the former occurs preceding changes in the latter.
authors.affiliation: Rockefeller University, New York, NY 10021.
authors.forename: H
authors.initials: H
authors.lastname: Fujita
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Yamagami
authors.forename: N
authors.initials: N
authors.lastname: Hayashi
authors.forename: T R
authors.initials: TR
authors.lastname: Bishop
authors.forename: H
authors.initials: H
authors.lastname: De Verneuil
authors.forename: T
authors.initials: T
authors.lastname: Yoshinaga
authors.forename: S
authors.initials: S
authors.lastname: Shibahara
authors.forename: R
authors.initials: R
authors.lastname: Morimoto
authors.forename: S
authors.initials: S
authors.lastname: Sassa
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation; D002472:Cell Transformation, Viral; D004912:Erythrocytes / Q000166:cytology*; D005622:Friend murine leukemia virus / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D006418:Heme / Q000378:metabolism*; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D006418:Heme