Histone acetylations mark origins of polycistronic transcription in Leishmania major.
Histone acetylations mark origins of polycistronic transcription in Leishmania major.
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DOI：
10.1186/1471-2164-10-152
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发表时间：
2009-04-08
期刊：
影响因子：
4.4
通讯作者：
Myler PJ
中科院分区：
文献类型：
--
作者：
Thomas S;Green A;Sturm NR;Campbell DA;Myler PJ
RNA聚合酶II转录机制的许多组成部分已被确定在动质体原生动物，但他们分歧很大，从其他真核生物。此外，这些生物体中的蛋白质编码基因缺乏单独的转录调控，因为它们被转录为长的多顺反子单位。转录起始位点被假定位于相对的多顺反子基因簇之间的连接处的“发散链开关”区域内。然而，动质体启动转录的机制尚不清楚，启动子序列也不确定。使用与通过染色质免疫沉淀（ChIP-芯片）获得的DNA杂交的微阵列，在硕大利什曼原虫中评估TATA结合蛋白（TBP或TRF 4）、小核活化蛋白复合物（SNAP 50）和H3组蛋白的染色体定位。TBP和SNAP 50结合模式几乎相同，并且高强度峰与tRNA和snRNA相关。在整个基因组中仅发现了184个乙酰化H3组蛋白峰，快速分裂细胞中的强度比静止期高得多。大多数乙酰化H3峰出现在不同的链转换区域，但也有一些出现在染色体末端和多顺反子基因簇内。几乎所有这些峰都与TBP/SNAP 50结合上游几个酶的较低强度峰相关，证明它们代表转录起始位点。第一个全基因组的DNA结合蛋白质占据的动质体生物体的地图表明，H3组蛋白的蛋白质编码基因的多顺反子转录的起源乙酰化。转录起始的全局调节可以通过改变这些起源的乙酰化状态来实现。
Many components of the RNA polymerase II transcription machinery have been identified in kinetoplastid protozoa, but they diverge substantially from other eukaryotes. Furthermore, protein-coding genes in these organisms lack individual transcriptional regulation, since they are transcribed as long polycistronic units. The transcription initiation sites are assumed to lie within the 'divergent strand-switch' regions at the junction between opposing polycistronic gene clusters. However, the mechanism by which Kinetoplastidae initiate transcription is unclear, and promoter sequences are undefined. The chromosomal location of TATA-binding protein (TBP or TRF4), Small Nuclear Activating Protein complex (SNAP50), and H3 histones were assessed in Leishmania major using microarrays hybridized with DNA obtained through chromatin immunoprecipitation (ChIP-chip). The TBP and SNAP50 binding patterns were almost identical and high intensity peaks were associated with tRNAs and snRNAs. Only 184 peaks of acetylated H3 histone were found in the entire genome, with substantially higher intensity in rapidly-dividing cells than stationary-phase. The majority of the acetylated H3 peaks were found at divergent strand-switch regions, but some occurred at chromosome ends and within polycistronic gene clusters. Almost all these peaks were associated with lower intensity peaks of TBP/SNAP50 binding a few kilobases upstream, evidence that they represent transcription initiation sites. The first genome-wide maps of DNA-binding protein occupancy in a kinetoplastid organism suggest that H3 histones at the origins of polycistronic transcription of protein-coding genes are acetylated. Global regulation of transcription initiation may be achieved by modifying the acetylation state of these origins.
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