Centre for Cellular and Molecular Biology, Hyderabad 500007, India.
BMC Genomics. 2009 Nov 20;10:549. doi: 10.1186/1471-2164-10-549.
Polycomb group (PcG) proteins maintain expression pattern of genes set early during development. Although originally isolated as regulators of homeotic genes, PcG members play a key role in epigenetic mechanism that maintains the expression state of a large number of genes. Polycomb (PC) is conserved during evolution and while invertebrates have one PC gene, vertebrates have five or more homologues. It remains unclear if different vertebrate PC homologues have distinct or overlapping functions. We have identified and compared the sequence of PC homologues in various organisms to analyze similarities and differences that shaped the evolutionary history of this key regulatory protein.
All PC homologues have an N-terminal chromodomain and a C-terminal Polycomb Repressor box. We searched the protein and genome sequence database of various organisms for these signatures and identified approximately 100 PC homologues. Comparative analysis of these sequences led to the identification of a novel insect specific motif and several novel and signature motifs in the vertebrate homologue: two in CBX2 (Cx2.1 and Cx2.2), four in CBX4 (Cx4.1, Cx4.2, Cx4.3 and Cx4.4), three in CBX6 (Cx6.1, Cx6.2 and Cx6.3) and one in CBX8 (Cx8.1). Additionally, adjacent to the chromodomain, all the vertebrate homologues have a DNA binding motif - AT-Hook in case of CBX2, which was known earlier, and 'AT-Hook Like' motif, from this study, in other PC homologues.
Our analysis shows that PC is an ancient gene dating back to pre bilaterian origin that has not only been conserved but has also expanded during the evolution of complexity. Unique motifs acquired by each homologue have been maintained for more than 500 millions years indicating their functional relevance in boosting the epigenetic 'tool kit'. We report the presence of a DNA interaction motif adjacent to chromodomain in all vertebrate PC homologues and suggest a three-way 'PC-histoneH3-DNA' interaction that can restrict nucleosome dynamics. The signature motifs of PC homologues and insect specific motif identified in this study pave the way to understand the molecular basis of epigenetic mechanisms.
多梳组（PcG）蛋白维持早期发育过程中基因表达模式。尽管最初作为同源盒基因的调节剂被分离出来，但 PcG 成员在维持大量基因表达状态的表观遗传机制中发挥着关键作用。多梳（PC）在进化过程中是保守的，而无脊椎动物只有一个 PC 基因，脊椎动物有五个或更多的同源物。不同的脊椎动物 PC 同源物是否具有不同或重叠的功能尚不清楚。我们已经鉴定并比较了各种生物体中 PC 同源物的序列，以分析塑造这种关键调节蛋白进化历史的相似性和差异性。
所有 PC 同源物都具有一个 N 端的 chromodomain 和一个 C 端的 Polycomb Repressor 盒。我们在各种生物体的蛋白质和基因组序列数据库中搜索这些特征，并鉴定了大约 100 个 PC 同源物。对这些序列的比较分析导致了在昆虫特异性motif 和脊椎动物同源物中的几个新的和特征性 motif 的鉴定：两个在 CBX2 中（Cx2.1 和 Cx2.2），四个在 CBX4 中（Cx4.1、Cx4.2、Cx4.3 和 Cx4.4），三个在 CBX6 中（Cx6.1、Cx6.2 和 Cx6.3），一个在 CBX8 中（Cx8.1）。此外，在 chromodomain 旁边，所有脊椎动物同源物都有一个 DNA 结合基序——在 CBX2 中是已知的 AT-Hook，而在其他 PC 同源物中则是本研究中新发现的“AT-Hook Like”基序。
我们的分析表明，PC 是一个古老的基因，可以追溯到前双侧起源，不仅在进化过程中得到了保守，而且还得到了扩展。每个同源物获得的独特 motif 已经保持了超过 5 亿年，表明它们在增强表观遗传“工具包”方面具有功能相关性。我们报告了所有脊椎动物 PC 同源物中 chromodomain 旁边存在 DNA 相互作用基序，并提出了一种三向“PC-histoneH3-DNA”相互作用，可限制核小体动力学。本研究中鉴定的 PC 同源物的特征 motif 和昆虫特异性 motif 为理解表观遗传机制的分子基础铺平了道路。
