The helix-loop-helix protein Id inhibits differentiation of murine erythroleukemia cells

Id is considered to be a negative regulator of basic helix-loop-helix proteins, which play important roles in cell type-specific transcription and cell lineage commitment. The Id gene was first cloned in murine erythroleukemia (MEL) cells, which can be induced to differentiate toward erythrocytes with Me2SO, and its mRNA decreases after differentiation in various types of cells. In this report, we demonstrate that overexpression of Id interferes with MEL cell differentiation and that inhibition of differentiation is accompanied by reduction in expression of three erythroid-specific genes. While down-regulation of Id is an early event in the differentiation process of MEL cells, E-box binding activity of these cells increases only at a later stage of differentiation, and this late increase is reduced by the overexpression of Id in the early stage. Sequential changes in the activity of several basic helix-loop-helix proteins thus appeared to be involved in erythroid differentiation.