Nègre Nicolas, Hennetin Jérôme, Sun Ling V, Lavrov Sergey, Bellis Michel, White Kevin P, Cavalli Giacomo
Institute of Human Genetics, Centre national de la recherche scientifique (CNRS), Montpellier Cedex, France.
PLoS Biol. 2006 Jun;4(6):e170. doi: 10.1371/journal.pbio.0040170. Epub 2006 Apr 20.
Polycomb group (PcG) proteins are able to maintain the memory of silent transcriptional states of homeotic genes throughout development. In Drosophila, they form multimeric complexes that bind to specific DNA regulatory elements named PcG response elements (PREs). To date, few PREs have been identified and the chromosomal distribution of PcG proteins during development is unknown. We used chromatin immunoprecipitation (ChIP) with genomic tiling path microarrays to analyze the binding profile of the PcG proteins Polycomb (PC) and Polyhomeotic (PH) across 10 Mb of euchromatin. We also analyzed the distribution of GAGA factor (GAF), a sequence-specific DNA binding protein that is found at most previously identified PREs. Our data show that PC and PH often bind to clustered regions within large loci that encode transcription factors which play multiple roles in developmental patterning and in the regulation of cell proliferation. GAF co-localizes with PC and PH to a limited extent, suggesting that GAF is not a necessary component of chromatin at PREs. Finally, the chromosome-association profile of PC and PH changes during development, suggesting that the function of these proteins in the regulation of some of their target genes might be more dynamic than previously anticipated.
多梳蛋白家族（PcG）能够在整个发育过程中维持同源异型基因沉默转录状态的记忆。在果蝇中，它们形成多聚体复合物，与名为多梳蛋白反应元件（PREs）的特定DNA调控元件结合。迄今为止，已鉴定出的PREs很少，且发育过程中PcG蛋白的染色体分布尚不清楚。我们使用染色质免疫沉淀（ChIP）结合基因组平铺路径微阵列来分析PcG蛋白多梳（PC）和多线同源框蛋白（PH）在10 Mb常染色质上的结合图谱。我们还分析了GAGA因子（GAF）的分布，GAF是一种序列特异性DNA结合蛋白，存在于大多数先前鉴定出的PREs中。我们的数据表明，PC和PH通常结合在大基因座内的簇状区域，这些基因座编码在发育模式形成和细胞增殖调控中发挥多种作用的转录因子。GAF与PC和PH在一定程度上共定位，这表明GAF不是PREs处染色质的必要组成部分。最后，PC和PH的染色体关联图谱在发育过程中发生变化，这表明这些蛋白在调控其某些靶基因时的功能可能比之前预期的更具动态性。
