Self-Regulation of Mouse p45/NF-E2 during Murine Erythroleukemia Cell Differentiation

Tung-Liang Lee, Shau-Ching Wen, Wei-Yuan Hsiao, Che-Kun James Shen, and Yu-Chiau Shyu (2009) Self-regulation of mouse p45/NF-E2 during murine erythroleukemia cell differentiation. Zoological Studies 48(3): 362-369. The complicated process of murine erythroleukemia (MEL) cell differentiation is precisely controlled by a group of transcription factors. One of those transcription factors, p45/NF-E2, is important for globin gene expression. We analyzed the structure of the mouse p45 gene which contains a putative nuclear factor erythroid-derived 2 (NF-E2) which binds to the Maf recognition element (MARE) located upstream of the erythroid-specific p45 promoter. Chromatin immunoprecipitation (ChIP) assays showed that p45/NF-E2 bound to this MARE-like region during the period of dimethyl sulfoxide (DMSO)-induced MEL differentiation. Moreover, the ChIP analysis also showed that p45/NF-E2 binding to the GATA-1 binding region of the erythroidspecific p45 promoter was similar to the binding to the MARE-like region. Analysis of the p45 expression profile corresponded to the p45 promoter binding capacity of p45/NF-E2 during MEL cell differentiation. This evidence suggests that the MARE-like binding site might function as an enhancer that interacts with the GATA-1 binding motif within the p45 promoter to mediate the upregulation of p45 mRNA in erythroid differentiation. Furthermore, we also found that the MARE binding repressor, Bach1, did not bind to the p45 promoter, thus excluding any involvement of Bach1 in p45 gene regulation before MEL differentiation. Together these results suggest that p45/NF-E2 self-regulation is a positive enhancer regulatory mechanism, which differs from the MAREdependent regulatory mechanism that contributes to the rapid upregulation of p45/NF-E2 required for erythroid differentiation. http://zoolstud.sinica.edu.tw/Journals/48.3/362.pdf