一項(xiàng)發(fā)表于Neuron雜志的研究報(bào)告稱(chēng),，老鼠細(xì)胞中一種能夠抑制基因活性的蛋白質(zhì)復(fù)合體如果功能出現(xiàn)異常，將導(dǎo)致老鼠出現(xiàn)智力遲鈍,。
雖然每個(gè)細(xì)胞所含的基因是相同的,，但越來(lái)越多的證據(jù)表明，基因的活性還受到組蛋白的控制,。組蛋白化學(xué)修飾可控制基因的開(kāi)啟和關(guān)閉,。研究表明，組蛋白化學(xué)修飾能夠產(chǎn)生一種獨(dú)特的表觀遺傳密碼,，從而調(diào)控細(xì)胞中特定基因的表達(dá)過(guò)程,。
該課題組對(duì)GLP/G9a酶進(jìn)行研究，哺乳動(dòng)物(包括人在內(nèi))中的GLP/G9a酶與基因表達(dá)沉默的表觀遺傳標(biāo)記有關(guān),。GLP/G9a酶能將兩個(gè)甲基群連接到組蛋白的特定的氨基酸上,，從而抑制基因的活性。該課題組研究人員建立了一種特殊的老鼠株系,，這類(lèi)老鼠能夠在一定條件下在不同細(xì)胞(包括大腦中的神經(jīng)元)中清除GLP/G9a蛋白質(zhì)復(fù)合體,。
研究人員對(duì)這組老鼠行為學(xué)測(cè)試發(fā)現(xiàn)，其行為表現(xiàn)類(lèi)似于一種人類(lèi)的智力遲鈍綜合癥——9q34缺失綜合癥,。缺失GLP/G9a酶的老鼠與正常老鼠相比,，不害怕開(kāi)放場(chǎng)所，易肥胖并且環(huán)境適應(yīng)能力較差,。
研究人員發(fā)現(xiàn),，缺失GLP/G9a酶將導(dǎo)致肌肉和心臟中某些基因表達(dá)量增加,。通常情況下,，這些基因被表觀遺傳標(biāo)簽所抑制，但在GLP/G9a酶缺失的條件下,，基因表達(dá)量增加,。研究人員推測(cè)，這可能是控制組蛋白H3甲基化標(biāo)簽的表觀遺傳調(diào)控因子的改變引起了老鼠出現(xiàn)學(xué)習(xí)和社會(huì)適應(yīng)能力降低,。（生物谷Bioon.com）
生物谷推薦原始出處：
Neuron, Volume 64, 10 December 2009 doi:10.1016/j.neuron.2009.11.019
Control of Cognition and Adaptive Behavior by the GLP/G9a Epigenetic Suppressor Complex
Anne Schaefer1, 4, Srihari C. Sampath2, 4, 6, Adam Intrator1, Alice Min1, Tracy S. Gertler3, D. James Surmeier3, Alexander Tarakhovsky2, 5, , and Paul Greengard1, 5, ,
1 Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
2 Laboratory of Lymphocyte Signaling, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
3 Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
The genetic basis of cognition and behavioral adaptation to the environment remains poorly understood. Here we demonstrate that the histone methyltransferase complex GLP/G9a controls cognition and adaptive responses in a region-specific fashion in the adult brain. Using conditional mutagenesis in mice, we show that postnatal, neuron-specific deficiency of GLP/G9a leads to derepression of numerous nonneuronal and neuron progenitor genes in adult neurons. This transcriptional alteration is associated with complex behavioral abnormalities, including defects in learning, motivation, and environmental adaptation. The behavioral changes triggered by GLP/G9a deficiency are similar to key symptoms of the human 9q34 mental retardation syndrome that is associated with structural alterations of the GLP/EHMT1 gene. The likely causal role of GLP/G9a in mental retardation in mice and humans suggests a key role for the GLP/G9a-controlled histone H3K9 dimethylation in regulation of brain function through maintenance of the transcriptional homeostasis in adult neurons.
