Histone deacetylase 11 (HDAC11) is the sole member of the class IV histone deacetylase family. It is a zinc-dependent lysine deacetylase whose classic function is to remove acetyl groups from histone tails, thereby compacting chromatin and repressing transcription. Beyond histones, HDAC11 also acts on non-histone substrates and has been reported to catalyze the removal of long-chain fatty acyl groups from lysine residues, suggesting a broader role at the intersection of epigenetic and metabolic regulation. This gene is highly conserved in vertebrates, is relatively small compared to other HDACs, and encodes an enzyme with a central catalytic pocket coordinated by Zn2+. HDAC11 is expressed in various tissues, with higher expression levels in the brain and testes, and its localization varies between the nucleus and cytoplasm depending on cell type and environment. Functionally, HDAC11 is involved in controlling immune responses (e.g., regulating cytokine secretion by antigen-presenting cells and T cell activation), influencing neuronal and oligodendrocyte biology, and shaping cellular metabolism (including lipid metabolism). In cancer models, dysregulation of HDAC11 is associated with altered cell proliferation, survival, and migration behaviors, and therefore HDAC11 is being investigated as a therapeutic target, with selective inhibitors currently under development.
The HDAC11 adenovirus is a replication-deficient human adenovirus type 5 (Ad5) vector with E1/E3 deletions, genetically engineered to express full-length human HDAC11 fused to a C-terminal V5 epitope tag under the control of the cytomegalovirus (CMV) immediate early promoter. This construct enables efficient and transient overexpression of HDAC11 in a variety of mammalian cell types, including many cell types that are difficult to transfect, and is suitable for in vitro and in vivo applications where Ad5 tropism is favorable. Typical applications focus on gain-of-function studies to elucidate the biological functions of HDAC11: researchers can assess chromatin changes by measuring overall or site-specific histone acetylation status, evaluate transcriptome remodeling through RNA sequencing, and assess proteome remodeling through proteomic analysis (including detecting changes in lysine acylation status on candidate substrates). The V5 tag facilitates sensitive detection and can be used for direct Western blotting, immunofluorescence (to determine subcellular localization), immunoprecipitation (to identify interaction partners), and V5-based chromatin analysis (to explore its recruitment to specific genomic regions).
Inhibition of histone deacetylase 11 (HDAC11) promotes IL-10 expression in mouse macrophages RAW264.7 and induces immune tolerance. Here, researchers investigated the role of HDAC11 in the induction of immune tolerance in Kupffer cells (KCs) after orthotopic liver transplantation (OLT) in rats. KCs isolated from BALB/c mice were divided into pHDAC11, adHDAC11, and pCV groups (treated with HADC11-shRNA, adenovirus encoding HDAC11, and control vector, respectively). After Ad-HDAC11 and pHDAC11 treatment, rats were subjected to OLT. In KCs, Ad-HDAC11 and HDAC11-shRNA inhibited and promoted IL-10 expression, respectively. Compared with the pCV group, MHC-II class molecules and co-stimulatory molecules on the surface of KCs and T cell proliferation were significantly inhibited and induced in the pHDAC11 and Ad-HDAC11 groups. Compared with the pCV group, the serum levels of IL-2, TNF-α, and IFN-γ in the pHDAC11 group were significantly decreased, while the serum levels of IL-4 and IL-10 in the Ad-HDAC11 group were significantly increased. These results suggest that inhibition of HDAC11 can promote the expression of IL-10 in KCs after rat liver transplantation and induce hepatocyte tolerance. Therefore, HDAC11 may be a key component of this immune regulatory system and a promising target for the development of new gene therapy drugs to induce tolerance in clinical liver transplantation.
Recipients were sacrificed to evaluate histologic changes at indicated time points. Light microscopy showed that the transplanted kidneys of rats in the Ad-HDAC11 group underwent acute rejection, while the rejection in the pHDAC11 group was mild (Figure 1). ALT (U/L) and TBIL (mmol/L) of rats in the Ad-HDAC11 group increased significantly, and ALB (g/L) decreased, indicating severe liver damage. However, the above liver function indicators of rats in the pHDAC11 group changed slightly, indicating that the liver damage of rats in the pHDAC11 pretreatment group was mild.
Figure 1. Pathologic alterations of each group at 3 d after OLT, light microscopy (LM) hematoxylin-eosin (HE) X400. (Lian Z, et al., 2012)
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Highly recommend for epigenetic research!
The HDAC11 adenovirus from Creative Biogene delivered outstanding transduction efficiency in our neuronal studies. The purity and titer were perfect, and the results were highly reproducible. Highly recommend for epigenetic research!
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