The myocyte enhancer factor (MEF2) family of transcription factors, originally discovered for its pivotal role in muscle development and function, has emerged as an essential regulator in various aspects of brain development and neuronal plasticity. The MEF2 transcription factors are known to regulate numerous important genes in the nervous system, including brain-derived neurotrophic factor (BDNF), a small secreted neurotrophin responsible for promoting the survival, growth, and differentiation of neurons. The expression of the gene is spatiotemporally controlled by various transcription factors binding to both its proximal and distal regulatory regions. While previous studies have investigated the connection between MEF2 transcription factors and , the endogenous function of MEF2 factors in the transcriptional regulation of remains largely unknown. Here, we aimed to deepen the knowledge of MEF2 transcription factors and their role in the regulation of comparatively in rat cortical and hippocampal neurons. As a result, we demonstrate that the MEF2 transcription factor-dependent enhancer located at −4.8 kb from the gene regulates the endogenous expression of in hippocampal neurons. In addition, we confirm neuronal activity-dependent activation of the −4.8 kb enhancer . Finally, we show that specific MEF2 family transcription factors have unique roles in the regulation of with the specific function varying based on the particular brain region and stimuli. Altogether, we present MEF2 family transcription factors as crucial regulators of expression, fine-tuning expression through both distal and proximal regulatory regions.

中文翻译：

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上游增强子和 MEF2 转录因子微调皮质和海马神经元中 Bdnf 基因的调节


肌细胞增强因子 (MEF2) 转录因子家族最初因其在肌肉发育和功能中的关键作用而被发现，现已成为大脑发育和神经元可塑性各个方面的重要调节因子。 MEF2 转录因子已知可调节神经系统中的许多重要基因，包括脑源性神经营养因子 (BDNF)，这是一种负责促进神经元存活、生长和分化的小型分泌性神经营养因子。该基因的表达受到与其近端和远端调节区结合的各种转录因子的时空控制。虽然之前的研究已经调查了 MEF2 转录因子 和 之间的联系，但 MEF2 因子在转录调控中的内源功能仍然很大程度上未知。在这里，我们的目的是加深对 MEF2 转录因子及其在大鼠皮质和海马神经元相对调节中的作用的了解。结果，我们证明位于该基因-4.8 kb 处的 MEF2 转录因子依赖性增强子调节海马神经元的内源表达。此外，我们确认了 -4.8 kb 增强子的神经元活动依赖性激活。最后，我们表明特定的 MEF2 家族转录因子在调节中具有独特的作用，其特定功能根据特定的大脑区域和刺激而变化。总而言之，我们将 MEF2 家族转录因子作为表达的关键调节因子，通过远端和近端调节区域微调表达。