Lawrence Berkeley National Laboratory, University of California, Berkeley, California, USA.
Mol Cell Biol. 2012 Jan;32(2):333-47. doi: 10.1128/MCB.05917-11. Epub 2011 Nov 7.
Complex behaviors, such as learning and memory, are associated with rapid changes in gene expression of neurons and subsequent formation of new synaptic connections. However, how external signals are processed to drive specific changes in gene expression is largely unknown. We found that the genome organizer protein Satb1 is highly expressed in mature neurons, primarily in the cerebral cortex, dentate hilus, and amygdala. In Satb1-null mice, cortical layer morphology was normal. However, in postnatal Satb1-null cortical pyramidal neurons, we found a substantial decrease in the density of dendritic spines, which play critical roles in synaptic transmission and plasticity. Further, we found that in the cerebral cortex, Satb1 binds to genomic loci of multiple immediate early genes (IEGs) (Fos, Fosb, Egr1, Egr2, Arc, and Bdnf) and other key neuronal genes, many of which have been implicated in synaptic plasticity. Loss of Satb1 resulted in greatly alters timing and expression levels of these IEGs during early postnatal cerebral cortical development and also upon stimulation in cortical organotypic cultures. These data indicate that Satb1 is required for proper temporal dynamics of IEG expression. Based on these findings, we propose that Satb1 plays a critical role in cortical neurons to facilitate neuronal plasticity.
复杂行为，如学习和记忆，与神经元基因表达的快速变化和随后新突触连接的形成有关。然而，外部信号如何被处理以驱动特定的基因表达变化在很大程度上是未知的。我们发现，基因组组织者蛋白 Satb1 在成熟神经元中高度表达，主要在大脑皮层、齿状回和杏仁核中表达。在 Satb1 缺失的小鼠中，皮质层形态正常。然而，在出生后 Satb1 缺失的皮质锥体细胞中，我们发现树突棘的密度显著降低，树突棘在突触传递和可塑性中起着关键作用。此外，我们发现 Satb1 在大脑皮层中结合到多个即时早期基因（IEGs）（Fos、Fosb、Egr1、Egr2、Arc 和 Bdnf）和其他关键神经元基因的基因组位置，其中许多基因与突触可塑性有关。Satb1 的缺失导致这些 IEG 在早期大脑皮层发育过程中和皮质器官型培养物中的刺激下的表达时间和表达水平发生了极大改变。这些数据表明 Satb1 是正确的 IEG 表达的时间动态所必需的。基于这些发现，我们提出 Satb1 在皮质神经元中发挥关键作用，以促进神经元可塑性。
