Krüger G, Huber M C, Bonifer C
Institut für Biologie III der Universität Freiburg, Schänzlestr.1, 79104, Freiburg, Germany.
Gene. 1999 Aug 5;236(1):63-77. doi: 10.1016/s0378-1119(99)00271-1.
Tissue specific regulation of the chicken lysozyme locus is achieved by a combination of positive and negative cis-regulatory elements. Here we describe the molecular characterization of a newly discovered enhancer element located -3.9kb upstream of the transcription start. The -3.9kb enhancer is activated early in macrophage differentiation, as indicated by chromatin reorganization in macrophage precursor cells. Interestingly, enhancer activation leads to nucleosome phasing. Tissue specificity of expression is achieved by a combination of 5'-sequences with ubiquitous enhancer activity and 3'-flanking sequences. The 5'-half contains binding sites for members of the nuclear factor I transcription family and a yet unknown protein. We could show by in vivo footprinting that the ubiquitously expressed factors occupy their binding sites only in lysozyme expressing cells. We conclude that a specific chromatin architecture may be responsible for the differential activity of the enhancer.
鸡溶菌酶基因座的组织特异性调控是通过正向和负向顺式调控元件的组合来实现的。在此，我们描述了一个新发现的增强子元件的分子特征，该元件位于转录起始点上游-3.9kb处。如巨噬细胞前体细胞中的染色质重组所示，-3.9kb增强子在巨噬细胞分化早期被激活。有趣的是，增强子激活导致核小体相位化。表达的组织特异性是通过具有普遍增强子活性的5'序列和3'侧翼序列的组合来实现的。5'端包含核因子I转录家族成员和一种未知蛋白质的结合位点。我们通过体内足迹法表明，普遍表达的因子仅在表达溶菌酶的细胞中占据其结合位点。我们得出结论，特定的染色质结构可能是增强子差异活性的原因。
