Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
J Cell Biochem. 2010 May;110(1):62-9. doi: 10.1002/jcb.22487.
Carboxy-terminal binding protein (CtBP) is a well-known corepressor of several DNA binding transcription factors in Drosophila as well as in mammals. CtBP is implicated in Polycomb Group (PcG) complex-mediated transcriptional repression because it can bind to some PcG proteins, and mutation of the ctbp gene in flies results in lost PcG protein recruitment to Polycomb Response Elements (PREs) and lost PcG repression. However, the mechanism of reduced PcG DNA binding in CtBP mutant backgrounds is unknown. We show here that in a Drosophila CtBP mutant background, intergenic transcripts are induced across several PRE sequences and this corresponds to reduced DNA binding by PcG proteins Pleiohomeotic (PHO) and Polycomb (Pc), and reduced trimethylation of histone H3 on lysine 27, a hallmark of PcG repression. Restoration of CtBP levels by expression of a CtBP transgene results in repression of intergenic transcripts, restored PcG binding, and elevated trimethylation of H3 on lysine 27. Our results support a model in which CtBP regulates expression of intergenic transcripts that controls DNA binding by PcG proteins and subsequent histone modifications and transcriptional activity.
羧基末端结合蛋白（CtBP）是果蝇以及哺乳动物中几种 DNA 结合转录因子的著名核心抑制子。CtBP 参与 Polycomb 组（PcG）复合物介导的转录抑制，因为它可以结合一些 PcG 蛋白，并且果蝇中 ctbp 基因突变会导致 PcG 蛋白募集到 Polycomb 反应元件（PREs）减少，PcG 抑制作用丧失。然而，CtBP 突变背景中 PcG DNA 结合减少的机制尚不清楚。我们在这里表明，在 Drosophila CtBP 突变背景中，几个 PRE 序列上的基因间转录物被诱导，这对应于 PcG 蛋白 Pleiohomeotic（PHO）和 Polycomb（Pc）的 DNA 结合减少，以及组蛋白 H3 赖氨酸 27 上三甲基化减少，这是 PcG 抑制的标志。通过表达 CtBP 转基因恢复 CtBP 水平可导致基因间转录物的抑制，PcG 结合恢复，以及组蛋白 H3 赖氨酸 27 上的三甲基化升高。我们的结果支持这样一种模型，即 CtBP 调节基因间转录物的表达，从而控制 PcG 蛋白的 DNA 结合以及随后的组蛋白修饰和转录活性。
