文章：

HoxA9、Meis1和Pbx蛋白在正常造血祖细胞和转化髓细胞中对c-myb基因表达的不同调控

Distinct regulation of c-myb gene expression by HoxA9, Meis1 and Pbx proteins in normal hematopoietic progenitors and transformed myeloid cells

原文发布日期：2012-06-29

DOI: 10.1038/bcj.2012.20

类型: Original Article

开放获取: 是

英文摘要：

The proto-oncogenic protein c-Myb is an essential regulator of hematopoiesis and is frequently deregulated in hematological diseases such as lymphoma and leukemia. To gain insight into the mechanisms underlying the aberrant expression of c-Myb in myeloid leukemia, we analyzed and compared c-myb gene transcriptional regulation using two cell lines modeling normal hematopoietic progenitor cells (HPCs) and transformed myelomonocytic blasts. We report that the transcription factors HoxA9, Meis1, Pbx1 and Pbx2 bind in vivo to the c-myb locus and maintain its expression through different mechanisms in HPCs and leukemic cells. Our analysis also points to a critical role for Pbx2 in deregulating c-myb expression in murine myeloid cells cotransformed by the cooperative activity of HoxA9 and Meis1. This effect is associated with an intronic positioning of epigenetic marks and RNA polymerase II binding in the orthologous region of a previously described alternative promoter for c-myb. Taken together, our results could provide a first hint to explain the abnormal expression of c-myb in leukemic cells.

摘要翻译： 

原癌蛋白c-Myb是造血过程的关键调控因子，在淋巴瘤和白血病等血液疾病中常出现表达异常。为探究c-Myb在髓系白血病中异常表达的作用机制，我们通过模拟正常造血祖细胞与转化型髓单核母细胞的两种细胞系，对c-myb基因的转录调控进行对比分析。研究发现转录因子HoxA9、Meis1、Pbx1和Pbx2在体内与c-myb基因座结合，并通过不同机制在造血祖细胞和白血病细胞中维持其表达。分析还表明，在HoxA9与Meis1协同作用转化的鼠髓系细胞中，Pbx2对c-myb表达的异常调控起关键作用。该效应与表观遗传标记的内含子定位及RNA聚合酶II在先前发现的c-myb替代启动子同源区域的结合有关。综上，我们的研究为解释c-myb在白血病细胞中的异常表达提供了初步线索。

原文链接：

Distinct regulation of c-myb gene expression by HoxA9, Meis1 and Pbx proteins in normal hematopoietic progenitors and transformed myeloid cells