Lau Mei Sheng, Schwartz Matthew G, Kundu Sharmistha, Savol Andrej J, Wang Peggy I, Marr Sharon K, Grau Daniel J, Schorderet Patrick, Sadreyev Ruslan I, Tabin Clifford J, Kingston Robert E
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Science. 2017 Mar 10;355(6329):1081-1084. doi: 10.1126/science.aah5403. Epub 2017 Mar 9.
Nucleosomes play important structural and regulatory roles by tightly wrapping the DNA that constitutes the metazoan genome. The Polycomb group (PcG) proteins modulate nucleosomes to maintain repression of key developmental genes, including genes whose temporal and spatial expression is tightly regulated to guide patterning of the anterior-posterior body axis. CBX2, a component of the mammalian Polycomb repressive complex 1 (PRC1), contains a compaction region that has the biochemically defined activity of bridging adjacent nucleosomes. Here, we demonstrate that a functional compaction region is necessary for proper body patterning, because mutating this region leads to homeotic transformations similar to those observed with PcG loss-of-function mutations. We propose that CBX2-driven nucleosome compaction is a key mechanism by which PcG proteins maintain gene silencing during mouse development.
核小体通过紧密包裹构成后生动物基因组的DNA发挥重要的结构和调节作用。多梳蛋白家族(PcG)蛋白调节核小体以维持关键发育基因的抑制状态,这些基因包括其时空表达受到严格调控以指导前后身体轴模式形成的基因。CBX2是哺乳动物多梳抑制复合物1(PRC1)的一个组成部分,包含一个压缩区域,该区域具有在生化上确定的桥接相邻核小体的活性。在这里,我们证明功能性压缩区域对于正确的身体模式形成是必需的,因为该区域的突变会导致同源异型转化,类似于PcG功能丧失突变所观察到的情况。我们提出,CBX2驱动的核小体压缩是PcG蛋白在小鼠发育过程中维持基因沉默的关键机制。