一项发表于Neuron杂志的研究报告称，老鼠细胞中一种能够抑制基因活性的蛋白质复合体如果功能出现异常，将导致老鼠出现智力迟钝。
虽然每个细胞所含的基因是相同的，但越来越多的证据表明，基因的活性还受到组蛋白的控制。组蛋白化学修饰可控制基因的开启和关闭。研究表明，组蛋白化学修饰能够产生一种独特的表观遗传密码，从而调控细胞中特定基因的表达过程。
该课题组对GLP/G9a酶进行研究，哺乳动物(包括人在内)中的GLP/G9a酶与基因表达沉默的表观遗传标记有关。GLP/G9a酶能将两个甲基群连接到组蛋白的特定的氨基酸上，从而抑制基因的活性。该课题组研究人员建立了一种特殊的老鼠株系，这类老鼠能够在一定条件下在不同细胞(包括大脑中的神经元)中清除GLP/G9a蛋白质复合体。
研究人员对这组老鼠行为学测试发现，其行为表现类似于一种人类的智力迟钝综合症——9q34缺失综合症。缺失GLP/G9a酶的老鼠与正常老鼠相比，不害怕开放场所，易肥胖并且环境适应能力较差。
研究人员发现，缺失GLP/G9a酶将导致肌肉和心脏中某些基因表达量增加。通常情况下，这些基因被表观遗传标签所抑制，但在GLP/G9a酶缺失的条件下，基因表达量增加。研究人员推测，这可能是控制组蛋白H3甲基化标签的表观遗传调控因子的改变引起了老鼠出现学习和社会适应能力降低。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
