Inhibition of an erythroid differentiation switch by the helix-loop-helix protein Id1.
The Id proteins function as negative regulators of basic-helix-loop-helix transcription factors, which play important roles in determination of cell lineage and in tissue-specific differentiation. Down-regulation of Id1 mRNA is associated with dimethyl sulfoxide-induced terminal differentiation of mouse erythroleukemia cells. To examine the significance of Id1 down-regulation in erythroid differentiation, we generated stable mouse erythroleukemia cell lines that constitutively express a "marked" form of the murine Id1 gene. Terminal erythroid differentiation was inhibited in these lines, as indicated by a block in activation of the erythroid-specific genes alpha-globin, beta-globin, and band 3 and continued proliferation in the presence of dimethyl sulfoxide. Interestingly, this block occurred even in the presence of normal levels of the lineage-specific transcription factors GATA-1, NF-E2, and EKLF. Constitutive expression of Id1 did not interfere with DNase I hypersensitivity at site HS2 of the locus control region, expression of the erythropoietin receptor gene, or down-regulation of the endogenous Id1 or c-myc genes. The differentiation block is reversible in these lines and can be rescued by fusion with human erythroleukemia cells. These findings suggest that in vivo, Id1 functions as an antagonist of terminal erythroid differentiation.
Lister
J
J
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138-2020, USA.
Forrester
W C
WC
Baron
M H
MH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D004247:DNA; D004268:DNA-Binding Proteins / Q000502:physiology*; D003851:Deoxyribonucleases / Q000378:metabolism; D015536:Down-Regulation; D004920:Erythropoiesis / Q000502:physiology*; D016259:Genes, myc; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D051379:Mice; D008969:Molecular Sequence Data; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002843:Chromatin; D004268:DNA-Binding Proteins; C497453:ID1 protein, human; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA; D003851:Deoxyribonucleases