Histone deacetylase 1 (HDAC1) is a key enzyme encoded by the HDAC1 gene and belongs to the class I HDAC family. It plays a key role in epigenetic regulation by removing acetyl groups from histones, thereby condensing chromatin structure and repressing gene transcription. HDAC1 is involved in a variety of cellular processes, including cell cycle progression, differentiation, apoptosis, and DNA repair. HDAC1 dysregulation is associated with a variety of diseases, especially cancer, neurodegenerative diseases, and inflammation. Due to its central role in the regulation of gene expression, HDAC1 is an important target for therapeutic intervention, and HDAC inhibitors are being explored as potential therapies for the treatment of malignancies and other diseases.
Human HDAC1 adenoviral particles are engineered viral vectors designed to efficiently deliver and express the HDAC1 gene in mammalian cells. These recombinant adenoviruses are replication-defective to ensure safety while maintaining high transduction efficiency in a variety of cell types, including primary cells and difficult-to-transfect cells. These viral particles carry the full-length human HDAC1 cDNA and are regulated by a strong promoter, resulting in stable and sustained protein expression. They are ideal for functional studies, such as investigating the role of HDAC1 in epigenetic regulation, cell signaling, or disease mechanisms. In addition, these viral particles are also valuable tools for gene therapy research, allowing scientists to explore the effects of HDAC1 overexpression or screen for HDAC inhibitors.
Overproduction of visceral fat is a major risk factor for many diseases. Inhibiting adipogenesis of mesenchymal stem cells (MSCs) would be an effective approach to prevent adipogenesis. Here, researchers elucidated that POU class 2 homeobox-related factor 1 (POU2AF1) may promote adipogenesis of MSCs through histone deacetylase 1 (HDAC1) signaling. Human retroperitoneal adipose-derived MSCs were isolated from overweight patients and controls. Overexpression and interference of POU2AF1 or HDAC1 were achieved using adenoviral transduction and cell small interfering RNA transfection. POU2AF1 expression was upregulated in the retroperitoneal adipose tissue of overweight patients and increased during adipogenesis. Overexpression of POU2AF1 promoted spontaneous adipogenesis without adipogenic treatment. Silencing of endogenous POU2AF1 in MSCs inhibited adipogenesis. POU2AF1 overexpression alleviated the translocation of HDAC1 to the nucleus, and the mRNA level of HDAC1 was also reduced. Co-transfection of Ad-POU2AF1 and Ad-HDAC1 partially reversed the promoting effect of POU2AF1 overexpression on spontaneous adipogenic differentiation of MSCs. POU2AF1 is involved in the natural differentiation of human mesenchymal stem cells, and overexpression or silencing of POU2AF1 can effectively induce or inhibit HDAC1 signal-mediated adipogenesis.
To determine whether HDAC1 is the main mediator of POU2AF1-regulated adipogenic differentiation, the researchers co-transfected Ad-POU2AF1 and Ad-HDAC1 and compared them with Ad-HDAC1 alone. Overexpression of HDAC1 was verified by Western blotting and real-time PCR analysis (Figure 1a-c). Co-transfection of Ad-POU2AF1 and Ad-HDAC1 partially reversed the promoting effect of POU2AF1 overexpression on spontaneous adipogenic differentiation of hASMCs (Figure 1d-g). The results showed that co-transfection of Ad-POU2AF1 and Ad-HDAC1 also reversed the protein and mRNA levels of PPARγ and C/EBPα, especially C/EBPα. These data indicate that HDAC1 is a downstream effector of POU2AF1-regulated adipogenic differentiation, while overexpression of HDAC1 alone has no such effect.
Figure 1. Overexpression of HDAC1 abolished the promotion effect of POU2AF1 on spontaneous adipogenic differentiation. (Wang Y, et al., 2021)
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07/25/2023
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