Polycomb Group (PcG)蛋白家族是一類進(jìn)化上極為保守的轉(zhuǎn)錄抑制因子，它們通過形成三種不同的蛋白復(fù)合物調(diào)控眾多重要生命活動(dòng)。2006年4月國(guó)際著名學(xué)術(shù)期刊Cell,、Science和Nature同時(shí)報(bào)道了PcG在胚胎干細(xì)胞全基因組范圍內(nèi)基因啟動(dòng)子區(qū)的富集情況,，認(rèn)為PcG蛋白家族是胚胎發(fā)育過程中一系列調(diào)控蛋白的掌控者（regulators’ regulator）,，但調(diào)控PcG蛋白的機(jī)制尚不清楚,。因此，新的PcG蛋白調(diào)節(jié)因子及調(diào)控機(jī)制研究成為發(fā)育生物學(xué)以及表觀遺傳學(xué)領(lǐng)域的熱點(diǎn),。
中國(guó)科學(xué)院上海生命科學(xué)研究院生物化學(xué)與細(xì)胞生物學(xué)研究所裴鋼院士領(lǐng)導(dǎo)的研究組經(jīng)過長(zhǎng)期研究發(fā)現(xiàn),，一種多功能的信號(hào)蛋白β-arrestin1在斑馬魚中高度保守，在斑馬魚中β-arrestin1的缺失會(huì)導(dǎo)致原始性造血異常,。他們的研究表明,，β-arrestin1能夠結(jié)合PcG招募蛋白YY1，通過影響YY1核質(zhì)定位解除PcG蛋白Suz12在cdx4, hoxa9a和hoxb4a等基因啟動(dòng)子區(qū)的富集和轉(zhuǎn)錄抑制作用,，最終促進(jìn)中胚層向造血細(xì)胞方向的分化。此項(xiàng)研究不僅首次揭示了信號(hào)蛋白β-arrestin1在脊椎動(dòng)物造血發(fā)育過程中的新功能,，而且發(fā)現(xiàn)了脊椎動(dòng)物體內(nèi)調(diào)控PcG蛋白功能的一種新機(jī)制,。上述研究成果得到同行評(píng)審專家的高度評(píng)價(jià)，認(rèn)為對(duì)理解調(diào)控PcG蛋白的機(jī)制具有促進(jìn)作用,。相關(guān)研究結(jié)果于2009年10月30日在線發(fā)表在國(guó)際著名學(xué)術(shù)期刊Cell雜志上,。
該項(xiàng)研究工作得到了國(guó)家科技部、國(guó)家自然科學(xué)基金委,、中國(guó)科學(xué)院,、上海市科委的經(jīng)費(fèi)支持以及國(guó)家斑馬魚模式動(dòng)物中心的大力支持。（生物谷Bioon.com）
裴剛最新研究成果：
Nature Immunology：非編碼小RNA在多發(fā)性硬化癥發(fā)生過程中作用機(jī)制
Nature：胰島素耐受/II型糖尿病發(fā)病機(jī)制研究
Nature Immunology：調(diào)節(jié)CD4＋T細(xì)胞凋亡和自身免疫的關(guān)鍵蛋白β-arrestin1
裴剛院士最新信息：
與中國(guó)生命科學(xué)并肩邁向世界前列——生物谷專訪Cell Research主編裴剛院士,，常務(wù)副主編李黨生博士
生物谷推薦原始出處：
Cell, Volume 139, Issue 3, 535-546, 30 October 2009 doi:10.1016/j.cell.2009.08.038
β-Arrestin1 Regulates Zebrafish Hematopoiesis through Binding to YY1 and Relieving Polycomb Group Repression
Rui Yue1, Jiuhong Kang1, 2, Cong Zhao1, Wenxiang Hu1, Yawei Tang1, Xiaosong Liu1 and Gang Pei1, 2, ,
1 Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences; Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China
2 School of Life Science and Technology, Tongji University, 200092, Shanghai, China
β-Arrestin1 is a multifunctional protein critically involved in signal transduction. Recently, it is also identified as a nuclear transcriptional regulator, but the underlying mechanisms and physiological significance remain to be explored. Here, we identified β-arrestin1 as an evolutionarily conserved protein essential for zebrafish development. Zebrafish embryos depleted of β-arrestin1 displayed severe posterior defects and especially failed to undergo hematopoiesis. In addition, the expression of cdx4, a critical regulator of embryonic blood formation, and its downstream hox genes were downregulated by depletion of β-arrestin1, while injection of cdx4, hoxa9a or hoxb4a mRNA rescued the hematopoietic defects. Further mechanistic studies revealed that β-arrestin1 bound to and sequestered the polycomb group (PcG) recruiter YY1, and relieved PcG-mediated repression of cdx4-hox pathway, thus regulating hematopoietic lineage specification. Taken together, this study demonstrated a critical role of β-arrestin1 during zebrafish primitive hematopoiesis, as well as an important regulator of PcG proteins and cdx4-hox pathway.
