The minimal promoter plays a major role in silencing of the galago γ-globin gene in adult erythropoiesis

Abstract

The human γ-globin gene and its orthologous galago γ-globin gene evolved from an ancestral ε-globin gene. In galago, expression of the γ-gene remained restricted to the embryonic stage of development, whereas in humans, expression of the γ-gene was recruited to the fetal stage. To localize the cis-elements responsible for this developmentally distinct regulation, we studied the expression patterns of the human γ-gene driven by either the human or the galago γ-promoters in transgenic mice. γ-gene transcription driven by either promoter reached similar levels in embryonic erythropoiesis. In adult erythropoiesis the γ-gene was silenced when controlled by the galago γ-promoter, but it was expressed at a high level when it was linked to the human γ-promoter. By a series of γ-promoter truncations the sequences required for the down-regulation of the galago γ-globin gene were localized to the minimal promoter. Furthermore, by interchanging the TATA, CCAAT, and CACCC elements between the human and galago minimal promoters we found that whereas each box made a developmentally distinctive contribution to γ-globin gene expression, the CACCC box was largely responsible for the down-regulation of the γ-gene in adult erythropoiesis.