7月5日，Cell Stem Cell雜志在線報(bào)道,，科學(xué)家發(fā)現(xiàn)了一種在干細(xì)胞和早期胚胎發(fā)育中發(fā)揮關(guān)鍵調(diào)節(jié)作用的非經(jīng)典多梳家族蛋白復(fù)合物,。
科學(xué)家已知多梳家族蛋白成員L3mbtl2與轉(zhuǎn)錄抑制和染色質(zhì)組裝有關(guān)，但尚未確定其生物學(xué)功能,。本研究顯示,，破壞L3mbtl2表達(dá)可導(dǎo)致胚胎不能完成原腸胚發(fā)育而致死的結(jié)果。與此相應(yīng)的是,，L3mbtl2敲除胚胎干細(xì)胞（ES細(xì)胞）的增殖和分化出現(xiàn)異常,。
L3mbtl2通過(guò)招募多梳蛋白抑制復(fù)合物1（PRC1）相關(guān)的復(fù)合物來(lái)調(diào)節(jié)基因表達(dá)。該復(fù)合物類似于已知的E2F6復(fù)合物,，包括G9A,， HDAC1，Ring1b等組分,。L3mbtl2常與 H3K9的二重甲基化,，組蛋白低乙酰化,，和H2AK119泛素化一同出現(xiàn)在靶基因的部位,，但這些修飾狀態(tài)則既不依賴于L3mbtl2的存在，也不足以抑制基因表達(dá)。
全基因組的研究顯示,，L3mbtl2依賴的抑制復(fù)合物主要調(diào)節(jié)那些不被經(jīng)典的PRC1和PRC2所抑制的基因的表達(dá),。然而，一些發(fā)育調(diào)節(jié)子可被L3mbtl2,、PRC1和PRC2所聯(lián)合抑制調(diào)節(jié),。總之,，本研究發(fā)現(xiàn)一種具有高度選擇性的,，非典型的PRC1家族復(fù)合物。它在ES細(xì)胞執(zhí)行正常功能和早期胚胎發(fā)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.
