Adipogenesis is regulated by a cascade of signals that drive transcriptional reprogramming in adipocytes. Here, we report that nuclear actin regulates the chromatin states that establish tissue specific expression during adipogenesis. To study the role of β-actin in adipocyte differentiation we conducted RNA-Sequencing on wild-type (WT) and β-actin knockout (KO) mouse embryonic fibroblasts (MEFs) after reprograming to adipocytes. We found β-actin depletion affects induction of several adipogenic genes during transcriptional reprograming. This impaired regulation of adipogenic genes is linked to reduced expression of the pioneer factor Cebpa and is rescued by reintroducing NLS-tagged β-actin. ATAC-Seq in KO MEFs revealed that actin-dependent reduction in Cebpa expression correlates with decreased chromatin accessibility and loss of chromatin association of the ATPase Brg1. This, in turn, impairs CEBPB's association with its Cebpa promoter-proximal binding site during adipogenesis. We propose a role for the nuclear β-actin pool in maintaining open chromatin for transcriptional reprogramming during adipogenic differentiation.

脂肪生成受一系列信号驱动，这些信号驱动脂肪细胞中的转录重编程。在这里，我们报告核肌动蛋白调节在脂肪形成过程中建立组织特异性表达的染色质状态。为了研究β-肌动蛋白在脂肪细胞分化中的作用，我们对重编程为脂肪细胞的野生型（WT）和β-肌动蛋白敲除（KO）小鼠胚胎成纤维细胞（MEF）进行了RNA测序。我们发现β-肌动蛋白耗竭会影响转录重编程过程中几个成脂基因的诱导。脂肪形成基因的这种调节受损与先驱因子Cebpa的表达降低有关，并通过重新引入NLS标记的β-肌动蛋白得以挽救。KO MEF中的ATAC-Seq显示Cebpa依赖肌动蛋白的减少表达与减少的染色质可及性和ATPase Brg1的染色质缔合相关性降低有关。反过来，这会削弱CEBPB在脂肪形成过程中与其Cebpa启动子-近端结合位点的结合。我们提出核β-肌动蛋白池在成脂分化过程中维持开放染色质用于转录重编程的作用。