Signal-dependent Regulation of Transcription by Histone Deacetylase 7 Involves Recruitment to Promyelocytic Leukemia Protein Nuclear Bodies

Abstract

Promyelocytic leukemia protein (PML) nuclear bodies (NBs) are dynamic subnuclear compartments that play roles in several cellular processes, including apoptosis, transcriptional regulation, and DNA repair. Histone deacetylase (HDAC) 7 is a potent corepressor that inhibits transcription by myocyte enhancer factor 2 (MEF2) transcription factors. We show here that endogenous HDAC7 and PML interact and partially colocalize in PML NBs. Tumor necrosis factor (TNF)-alpha treatment recruits HDAC7 to PML NBs and enhances association of HDAC7 with PML in human umbilical vein endothelial cells. Consequently, TNF-alpha promotes dissociation of HDAC7 from MEF2 transcription factors and the promoters of MEF2 target genes such as matrix metalloproteinase (MMP)-10, leading to accumulation of MMP-10 mRNA. Conversely, knockdown of PML enhances the association between HDAC7 and MEF2 and decreases MMP-10 mRNA accumulation. Accordingly, ectopic expression of PML recruits HDAC7 to PML NBs and leads to activation of MEF2 reporter activity. Notably, small interfering RNA knockdown of PML decreases basal and TNF-alpha-induced MMP-10 mRNA accumulation. Our results reveal a novel mechanism by which PML sequesters HDAC7 to relieve repression and up-regulate gene expression.

PML-IV functions as a negative regulator of telomerase by interacting with TERT

“…(C) Telomerase activity of the PML-IV-stable cell lines. The extracts of H1299, mock, or stable cell lines were tested for telomerase activity as described in recruit several proteins, including CBP, p53, Hdm2 (MDM2), PIN1, HDAC7 and HCMV IE1, suggesting that unSUMOylated primary PML-NBs still have an important biological function (Bischof et al, 2002;Gao et al, 2008;Kang et al, 2006;Lallemand-Breitenbach et al, 2001;Reineke et al, 2008;Wei et al, 2003). Indeed, SUMOylation of PML is dispensable for premature senescence induced by p53, because PML3M can induce growth arrest and senescence (Bischof et al, 2002).…”

Monoubiquitination of Filamin B Regulates Vascular Endothelial Growth Factor-Mediated Trafficking of Histone Deacetylase 7

“…Transient transfections and luciferase assays were performed in 48-well culture plates according to our previously published protocol (22). HeLa cells were transfected with an muscle creatine kinase (MCK) promoter-containing reporter construct and CMX-␤-galactosidase (CMX-␤-Gal) expression plasmids.…”

“…Indirect immunofluorescence microscopy was conducted according to our published protocol (22). The cells were plated onto coverslips of 12-well plates and transfected using Lipofectamine 2000 (Invitrogen) according to the manufacturer's protocol.…”

“…Transient transfection and coimmunoprecipitation were carried out according to our published protocol (22). Cells were transfected with 1 to 10 g of the appropriate plasmids using Lipofectamine 2000 (Invitrogen) or transfected with targeting siRNAs or nontargeting siRNAs using DharmaFECT 1 (Dharmacon).…”

Mitogen-activated Protein Kinase Extracellular Signal-regulated Kinase 2 Phosphorylates and Promotes Pin1 Protein-dependent Promyelocytic Leukemia Protein Turnover

“…Viral infection also results in degradation of PML protein and disruption of the PML NBs (26,27). We have previously demonstrated that tumor necrosis factor ␣ (TNF␣) significantly induces PML accumulation in human umbilical vascular endothelial cells (28) and that HDAC7 is critical for TNF␣-induced NB formation by modulating PML SUMOylation (29). We also reported that PML interacts with the peptidyl-prolyl cis-trans isomerase, Pin1, in a phosphorylation-dependent manner and that this interaction promotes PML degradation (30).…”