Neuronal and Muscle Differentiation of Mammalian Cells Is Accompanied by a Change in PHF10 Isoform Expression.

The PBAF chromatin remodeling complex of the SWI/SNF family plays a critical role in the regulation of gene expression during tissue differentiation and organism development. The subunits of the PBAF complex have domains responsible for binding to N-terminal histone sequences. It determines the specificity of binding of the complex to chromatin. PHF10, a specific subunit of the PBAF complex, contains a DPF domain, which is a unique chromatin interaction domain. A PHF10 isoform that lacks the DPF domain is also present in vertebrate cells. This work shows that during neuronal and muscle differentiation of human and mouse cells, the expression of PHF10 isoforms changes: the form that does not have DPF replaces the form in which it is present. Replacement of PHF10 isoforms in the PBAF complex may affect its selectivity in the regulation of genes in differentiating cells.

[PHF10, a Subunit of the PBAF Chromatin Remodeling Complex, Changes Its Localization and Interacts with c-FOS during the Initiation of Long-Term Potentiation in Neuronal Culture].

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.

Stability of Chromatin Remodeling Complex Subunits Is Determined by Their Phosphorylation Status.

It was found that, in the differentiated cells of mouse brain, the level of core (Brg1 and BAF155) and specific (BRD7, BAF180, and PHF10) subunits of the chromatin-remodeling complex PBAF is reduced compared to the undifferentiated proliferating cells. Phosphorylation of PBAF complex subunits is required for maintaining their stability in differentiated brain cells.