7月5日，Cell Stem Cell杂志在线报道，科学家发现了一种在干细胞和早期胚胎发育中发挥关键调节作用的非经典多梳家族蛋白复合物。
科学家已知多梳家族蛋白成员L3mbtl2与转录抑制和染色质组装有关，但尚未确定其生物学功能。本研究显示，破坏L3mbtl2表达可导致胚胎不能完成原肠胚发育而致死的结果。与此相应的是，L3mbtl2敲除胚胎干细胞（ES细胞）的增殖和分化出现异常。
L3mbtl2通过招募多梳蛋白抑制复合物1（PRC1）相关的复合物来调节基因表达。该复合物类似于已知的E2F6复合物，包括G9A， HDAC1，Ring1b等组分。L3mbtl2常与 H3K9的二重甲基化，组蛋白低乙酰化，和H2AK119泛素化一同出现在靶基因的部位，但这些修饰状态则既不依赖于L3mbtl2的存在，也不足以抑制基因表达。
全基因组的研究显示，L3mbtl2依赖的抑制复合物主要调节那些不被经典的PRC1和PRC2所抑制的基因的表达。然而，一些发育调节子可被L3mbtl2、PRC1和PRC2所联合抑制调节。总之，本研究发现一种具有高度选择性的，非典型的PRC1家族复合物。它在ES细胞执行正常功能和早期胚胎发育中具有重要作用。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
PMC:
PMID:
The Polycomb Group Protein L3mbtl2 Assembles an Atypical PRC1-Family Complex that Is Essential in Pluripotent Stem Cells and Early Development
Jinzhong Qin, Warren A. Whyte, Endre Anderssen, Effie Apostolou, Hsu-Hsin Chen, Schahram Akbarian, Roderick T. Bronson, Konrad Hochedlinger, Sridhar Ramaswamy, Richard A. Young, Hanno Hock
L3mbtl2 has been implicated in transcriptional repression and chromatin compaction but its biological function has not been defined. Here we show that disruption of L3mbtl2 results in embryonic lethality with failure of gastrulation. This correlates with compromised proliferation and abnormal differentiation of L3mbtl2/ embryonic stem (ES) cells. L3mbtl2 regulates genes by recruiting a Polycomb Repressive Complex1 (PRC1)-related complex, resembling the previously described E2F6-complex, and including G9A, Hdac1, and Ring1b. The presence of L3mbtl2 at target genes is associated with H3K9 dimethylation, low histone acetylation, and H2AK119 ubiquitination, but the latter is neither dependent on L3mbtl2 nor sufficient for repression. Genome-wide studies revealed that the L3mbtl2-dependent complex predominantly regulates genes not bound by canonical PRC1 and PRC2. However, some developmental regulators are repressed by the combined activity of all three complexes. Together, we have uncovered a highly selective, essential role for an atypical PRC1-family complex in ES cells and early development.
