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Histone deacetylase (HDAC) inhibitors with a novel connecting unit linker region reveal a selectivity profile for HDAC4 and HDAC5 with improved activity against chemoresistant cancer cells.
In brief, it has been demonstrated that epigenetic factors, such as hypermethylation in HDAC4, HDAC5, and HDAC6 gene promoters, down-regulation in miR424/ 503, up-regulation of miR21, miR143, miR210, miR27a, and miR130/301, and upregulation of ion channels could display a potential function in molecular pathways alterations implicated in endothelial dysfunction in PAH (90).
Liu et al., "A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans," Journal of Clinical Investigation, vol.
Additionally, the mRNA levels of HDAC5, DNMT1, and DNMT3a in the hippocampus were assessed following the chronic administration of olanzapine and haloperidol to rats that were either exposed or not exposed to 21 d of chronic restraint stress.
Ferguson et al., "Inflammatory cytokines epigenetically regulate rheumatoid arthritis fibroblast-like synoviocyte activation by suppressing HDAC5 expression," Annals of the Rheumatic Diseases, vol.
HDACs can be divided into four distinct families, of particular interest are class I (HDAC1, HDAC2, HDAC5, and HDAC8) and class II (HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10) HDACs .
In glioblastoma, the expression of HDAC1 and HDAC3 is inversely correlated with survival of GB patients, whereas that of HDAC4, HDAC5, HDAC6, and HDAC11 is positively correlated with survival of glioma patients .
In fact, Class II histone deacetylases, HDAC4 and HDAC5, normally interfere with DNA binding of prohypertrophic transcription factors, such as NFAT, myocyte enhancement factor (MEF), and GATA-4.
Bading, "Neuronal activity-dependent nucleocytoplasmic shuttling of HDAC4 and HDAC5," Journal of Neurochemistry, vol.
Molecular mechanism of transcriptional repression of AhR repressor involving ANKRA2, HDAC4, and HDAC5. Biochem Biophys Res Commun 364:276-282.
(108) found that stress due to social rejection inhibits expression of BDNF in the rodent's hippocampus and increases methylation of histone H3-K27; whereas imipramine reverts the effect on BDNF at inhibiting the expression of deacetylase-5 (Hdac5) histone subsequently generating increase in the acetylation of H3 histone.
The wild-type and mutation-type allele frequencies of the 15 SNPs identified in the genes DNMT1, DNMT3a, DNMT3b, Ago2, HDAC5, CAPN1, and PRKAG3 in all 14 breeds of cattle are shown in Figure 2.
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