Brown J Lesley, Fritsch Cornelia, Mueller Jürg, Kassis Judith A
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Development. 2003 Jan;130(2):285-94. doi: 10.1242/dev.00204.
Polycomb group proteins (PcG) repress homeotic genes in cells where these genes must remain inactive during Drosophila and vertebrate development. This repression depends on cis-acting silencer sequences, called Polycomb group response elements (PREs). Pleiohomeotic (Pho), the only known sequence-specific DNA-binding PcG protein, binds to PREs but pho mutants show only mild phenotypes compared with other PcG mutants. We characterize pho-like, a gene encoding a protein with high similarity to Pho. Pho-like binds to Pho-binding sites in vitro and pho-like, pho double mutants show more severe misexpression of homeotic genes than do the single mutants. These results suggest that Pho and Pho-like act redundantly to repress homeotic genes. We examined the distribution of five PcG proteins on polytene chromosomes from pho-like, pho double mutants. Pc, Psc, Scm, E(z) and Ph remain bound to polytene chromosomes at most sites in the absence of Pho and Pho-like. At a few chromosomal locations, however, some of the PcG proteins are no longer present in the absence of Pho and Pho-like, suggesting that Pho-like and Pho may anchor PcG protein complexes to only a subset of PREs. Alternatively, Pho-like and Pho may not participate in the anchoring of PcG complexes, but may be necessary for transcriptional repression mediated through PREs. In contrast to Pho and Pho-like, removal of Trithorax-like/GAGA factor or Zeste, two other DNA-binding proteins implicated in PRE function, does not cause misexpression of homeotic genes or reporter genes in imaginal disks.
多梳蛋白家族（PcG）在果蝇和脊椎动物发育过程中，于那些必须保持无活性的细胞中抑制同源异型基因。这种抑制作用依赖于顺式作用沉默子序列，即多梳蛋白家族反应元件（PREs）。多梳蛋白（Pho）是唯一已知的序列特异性DNA结合PcG蛋白，它能与PREs结合，但与其他PcG突变体相比，pho突变体仅表现出轻微的表型。我们鉴定了pho样基因，它编码一种与Pho高度相似的蛋白质。pho样蛋白在体外能与Pho结合位点结合，且pho样、pho双突变体比单突变体表现出更严重的同源异型基因错误表达。这些结果表明，Pho和pho样蛋白在抑制同源异型基因方面发挥冗余作用。我们检测了来自pho样、pho双突变体的多线染色体上五种PcG蛋白的分布情况。在没有Pho和pho样蛋白的情况下，Pc、Psc、Scm、E(z)和Ph在大多数位点仍与多线染色体结合。然而，在一些染色体位置，在没有Pho和pho样蛋白时，一些PcG蛋白不再存在，这表明pho样蛋白和Pho可能仅将PcG蛋白复合物锚定到一部分PREs上。或者，pho样蛋白和Pho可能不参与PcG复合物的锚定，但可能是通过PREs介导的转录抑制所必需的。与Pho和pho样蛋白不同，去除另外两种与PRE功能相关的DNA结合蛋白三胸样蛋白/GAGA因子或Zeste，不会导致成虫盘同源异型基因或报告基因的错误表达。
