Bangsow C, Rubins N, Glusman G, Bernstein Y, Negreanu V, Goldenberg D, Lotem J, Ben-Asher E, Lancet D, Levanon D, Groner Y
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 76100, Israel.
Gene. 2001 Nov 28;279(2):221-32. doi: 10.1016/s0378-1119(01)00760-0.
The RUNX3 gene belongs to the runt domain family of transcription factors that act as master regulators of gene expression in major developmental pathways. In mammals the family includes three genes, RUNX1, RUNX2 and RUNX3. Here, we describe a comparative analysis of the human chromosome 1p36.1 encoded RUNX3 and mouse chromosome 4 encoded Runx3 genomic regions. The analysis revealed high similarities between the two genes in the overall size and organization and showed that RUNX3/Runx3 is the smallest in the family, but nevertheless exhibits all the structural elements characterizing the RUNX family. It also revealed that RUNX3/Runx3 bears a high content of the ancient mammalian repeat MIR. Together, these data delineate RUNX3/Runx3 as the evolutionary founder of the mammalian RUNX family. Detailed sequence analysis placed the two genes at a GC-rich H3 isochore with a sharp transition of GC content between the gene sequence and the downstream intergenic region. Two large conserved CpG islands were found within both genes, one around exon 2 and the other at the beginning of exon 6. RUNX1, RUNX2 and RUNX3 gene products bind to the same DNA motif, hence their temporal and spatial expression during development should be tightly regulated. Structure/function analysis showed that two promoter regions, designated P1 and P2, regulate RUNX3 expression in a cell type-specific manner. Transfection experiments demonstrated that both promoters were highly active in the GM1500 B-cell line, which endogenously expresses RUNX3, but were inactive in the K562 myeloid cell line, which does not express RUNX3.
RUNX3基因属于转录因子的 runt 结构域家族，在主要发育途径中作为基因表达的主要调节因子。在哺乳动物中，该家族包括三个基因，即RUNX1、RUNX2和RUNX3。在此，我们描述了对人类1号染色体p36.1编码的RUNX3和小鼠4号染色体编码的Runx3基因组区域的比较分析。分析揭示了这两个基因在整体大小和组织上高度相似，表明RUNX3/Runx3是该家族中最小的，但仍具有RUNX家族的所有结构特征。分析还表明RUNX3/Runx3含有高比例的古老哺乳动物重复序列MIR。这些数据共同将RUNX3/Runx3描绘为哺乳动物RUNX家族的进化起源。详细的序列分析将这两个基因定位在富含GC的H3等臂染色体上，基因序列与下游基因间区域的GC含量有明显转变。在这两个基因中都发现了两个大的保守CpG岛，一个在第2外显子周围，另一个在第6外显子起始处。RUNX1、RUNX2和RUNX3基因产物结合相同的DNA基序，因此它们在发育过程中的时空表达应受到严格调控。结构/功能分析表明，两个启动子区域，分别命名为P1和P2，以细胞类型特异性方式调节RUNX3的表达。转染实验表明，这两个启动子在GM1500 B细胞系中都具有高活性，该细胞系内源性表达RUNX3，但在不表达RUNX3的K562髓系细胞系中无活性。
