Azieva A M, Sheynov A A, Kirillova D A, Tatarskiy E V, Georgieva S G, Soshnikova N V
Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia.
Kurchatov Institute National Research Center, Moscow, 123182 Russia.
Mol Biol (Mosk). 2021 Nov-Dec;55(6):1021-1029. doi: 10.31857/S0026898421060033.
The PBAF chromatin remodeling complex interacts with many transcriptional activators and is recruited to target chromatin regions. PBAF plays an important role in maintaining and modifying the chromatin structure in mammalian cells. A subunit of the PBAF complex, the PHF10 transcription factor, is required for proliferation of neuronal precursors in the early stages of mouse brain development and gene expression in differentiated neurons. We showed that PHF10 interacts with the protein product of the early response gene </>c-FOS, the c-FOS transcriptional activator, which is expressed in response to the induction of long-term potentiation (LTP). LTP induction triggers the transcription of genes and the synthesis of proteins that provide changes that lead to the establishment of long-term contacts between neurons. We showed that in cells in differentiated neuronal culture, after the induction of LTP, expression of c-FOS, which is initially localized in the cytoplasm and then moves to the nucleus, begins. PHF10 is expressed in neuronal cells prior to LTP induction and has nuclear localization. However, 1 h after LTP induction, PHF10 is detected in the cytoplasm together with c-FOS, and then moves into the nucleus with it. Importantly, this behavior of PHF10 in response to KC1 stimulation is specific for neuronal cultures. It is assumed that during LTP, PHF10 together with c-FOS participates in the activation of secondary response genes that regulate the maintenance of plastic modifications and homeostasis of neuronal synapses. The PHF10 export from the nucleus and its rapid return together with c-FOS to the nucleus is possibly necessary for the rapid modulation of expression of target secondary response genes during LTP.
PBAF染色质重塑复合物与许多转录激活因子相互作用,并被招募到目标染色质区域。PBAF在维持和修饰哺乳动物细胞的染色质结构中起重要作用。PBAF复合物的一个亚基,即PHF10转录因子,是小鼠脑发育早期神经元前体增殖和分化神经元中基因表达所必需的。我们发现PHF10与早期反应基因c-FOS的蛋白质产物相互作用,c-FOS是一种转录激活因子,其表达是对长时程增强(LTP)诱导的响应。LTP诱导触发基因转录和蛋白质合成,这些变化导致神经元之间建立长期联系。我们发现,在分化的神经元培养细胞中,LTP诱导后,最初定位于细胞质然后转移到细胞核的c-FOS开始表达。PHF10在LTP诱导之前就在神经元细胞中表达并具有核定位。然而,LTP诱导1小时后,PHF10与c-FOS一起在细胞质中被检测到,然后与之一同进入细胞核。重要的是,PHF10对KCl刺激的这种反应行为在神经元培养中是特异性的。据推测,在LTP期间,PHF10与c-FOS一起参与调节神经元突触可塑性修饰和稳态维持的次级反应基因的激活。在LTP期间,PHF10从细胞核输出并与c-FOS一起迅速返回细胞核,这可能是快速调节目标次级反应基因表达所必需的。