Key Specifications Table
|Species Reactivity||Key Applications|
|H, M||WB, ChIP|
|Presentation||Anti-HDAC1 (mouse monoclonal IgG1,supernatant). One vial containing 40 μL of culture supernatant with 0.05% sodium azide. Store at -20°C.
Negative ChIP Control Supernatant. One vial containing 40 uL of mouse IgG containing supernatant with 0.05% sodium azide. Store at -20°C.
ChIP Primers p21. One vial containing 75 μL of 5 μM of each primer specific for a region of the human p21 (WAF1/CIP1/CDKN1A) promoter. Store at -20°C.
P21 Forward: CCC ACA GCA GAG GAG AAA GAA
P21 Reverse: CTG GAA ATC TCT GCC CAG ACA
|Safety Information according to GHS|
|Storage and Shipping Information|
|Storage Conditions||Stable for 1 year at -20°C from date of receipt|
|Material Size||10 assays|
|Material Package||10 assays per kit, ~4μL per chromatin immunoprecipitation|
ChIPAb+ HDAC1 - ChIP Validated Antibody and Primer Set SDS
|ChIPAb+ HDAC1 - 2420464||2420464|
|ChIPAb+ HDAC1 - 1959310||1959310|
|ChIPAb+ HDAC1 - 2016024||2016024|
|ChIPAb+ HDAC1 - 2089141||2089141|
|ChIPAb+ HDAC1 - 2194150||2194150|
|ChIPAb+ HDAC1 - 3386033||3386033|
|ChIPAb+ HDAC1 - DAM1663272||DAM1663272|
|ChIPAb+ HDAC1 - DAM1732843||DAM1732843|
|ChIPAb+ HDAC1 - DAM1754489||DAM1754489|
|ChIPAb+ HDAC1 - DAM1764572||DAM1764572|
|Reference overview||Pub Med ID|
|Knockdown of menin affects pre-mRNA processing and promoter fidelity at the interferon-gamma inducible IRF1 gene.|
Auriemma, LB; Shah, S; Linden, LM; Henriksen, MA
Epigenetics & chromatin 5 2 2012
The tumor suppressor menin (MEN1) is mutated in the inherited disease multiple endocrine neoplasia type I, and has several documented cellular roles, including the activation and repression of transcription effected by several transcription factors. As an activator, MEN1 is a component of the Set1-like mixed lineage leukemia (MLL) MLL1/MLL2 methyltransferase complex that methylates histone H3 lysine 4 (H3K4). MEN1 is localized to the signal transducer and activator of transcription 1 (STAT1)-dependent gene, interferon regulatory factor 1 (IRF1), and is further recruited when IRF1 transcription is triggered by interferon-γ signaling.RNAi-mediated knockdown of MEN1 alters the H3K4 dimethylation and H3 acetylation profiles, and the localization of histone deacetylase 3, at IRF1. While MEN1 knockdown does not impact the rate of transcription, IRF1 heteronuclear transcripts become enriched in MEN1-depleted cells. The processed mRNA and translated protein product are concomitantly reduced, and the antiviral state is attenuated. Additionally, the transcription start site at the IRF1 promoter is disrupted in the MEN1-depleted cells. The H3K4 demethylase, lysine specific demethylase 1, is also associated with IRF1, and its inhibition alters H3K4 methylation and disrupts the transcription start site as well.Taken together, the data indicate that MEN1 contributes to STAT1-activated gene expression in a novel manner that includes defining the transcription start site and RNA processing.
|cAMP-responsive element modulator (CREM)α protein signaling mediates epigenetic remodeling of the human interleukin-2 gene: implications in systemic lupus erythematosus.|
Hedrich, Christian M, et al.
J. Biol. Chem., 286: 43429-36 (2011) 2011
IL-2 is a key cytokine during proliferation and activation of T lymphocytes and functions as an auto- and paracrine growth factor. Regardless of activating effects on T lymphocytes, the absence of IL-2 has been linked to the development of autoimmune pathology in mice and humans. Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease and characterized by dysregulation of lymphocyte function, transcription factor and cytokine expression, and antigen presentation. Reduced IL-2 expression is a hallmark of SLE T lymphocytes and results in decreased numbers of regulatory T lymphocytes which play an important role in preventing autoimmunity. Reduced IL-2 expression was linked to overproduction of the transcription regulatory factor cAMP-responsive element modulator (CREM)α in SLE T lymphocytes and subsequent CREMα binding to a CRE site within the IL2 promoter (-180 CRE). In this study, we demonstrate the involvement of CREMα-mediated IL2 silencing in T lymphocytes from SLE patients through a gene-wide histone deacetylase 1-directed deacetylation of histone H3K18 and DNA methyltransferase 3a-directed cytosine phosphate guanosine (CpG)-DNA hypermethylation. For the first time, we provide direct evidence that CREMα mediates silencing of the IL2 gene in SLE T cells though histone deacetylation and CpG-DNA methylation.
|cAMP-responsive element modulator (CREM)α protein induces interleukin 17A expression and mediates epigenetic alterations at the interleukin-17A gene locus in patients with systemic lupus erythematosus.|
Rauen, Thomas, et al.
J. Biol. Chem., 286: 43437-46 (2011) 2011
IL-17A is a proinflammatory cytokine that is produced by specialized T helper cells and contributes to the development of several autoimmune diseases such as systemic lupus erythematosus (SLE). Transcription factor cAMP-responsive element modulator (CREM)α displays increased expression levels in T cells from SLE patients and has been described to account for aberrant T cell function in SLE pathogenesis. In this report, we provide evidence that CREMα physically binds to a cAMP-responsive element, CRE (-111/-104), within the proximal human IL17A promoter and increases its activity. Chromatin immunoprecipitation assays reveal that activated naïve CD4(+) T cells as well as T cells from SLE patients display increased CREMα binding to this site compared with T cells from healthy controls. The histone H3 modification pattern at the CRE site (-111/-104) and neighboring conserved noncoding sequences within the human IL17A gene locus suggests an accessible chromatin structure (H3K27 hypomethylation/H3K18 hyperacetylation) in activated naïve CD4(+) T cells and SLE T cells. H3K27 hypomethylation is accompanied by decreased cytosine phosphate guanosine (CpG)-DNA methylation in these regions in SLE T cells. Decreased recruitment of histone deacetylase (HDAC)1 and DNA methyltransferase (DNMT)3a to the CRE site (-111/-104) probably accounts for the observed epigenetic alterations. Reporter studies confirmed that DNA methylation of the IL17A promoter indeed abrogates its inducibility. Our findings demonstrate an extended role for CREMα in the immunopathogenesis of SLE because it contributes to increased expression of IL-17A.
|A highly conserved SOX6 double binding site mediates SOX6 gene downregulation in erythroid cells.|
Cantu', C; Grande, V; Alborelli, I; Cassinelli, L; Cantu', I; Colzani, MT; Ierardi, R; Ronzoni, L; Cappellini, MD; Ferrari, G; Ottolenghi, S; Ronchi, A
Nucleic acids research 39 486-501 2011
The Sox6 transcription factor plays critical roles in various cell types, including erythroid cells. Sox6-deficient mice are anemic due to impaired red cell maturation and show inappropriate globin gene expression in definitive erythrocytes. To identify new Sox6 target genes in erythroid cells, we used the known repressive double Sox6 consensus within the εy-globin promoter to perform a bioinformatic genome-wide search for similar, evolutionarily conserved motifs located within genes whose expression changes during erythropoiesis. We found a highly conserved Sox6 consensus within the Sox6 human gene promoter itself. This sequence is bound by Sox6 in vitro and in vivo, and mediates transcriptional repression in transient transfections in human erythroleukemic K562 cells and in primary erythroblasts. The binding of a lentiviral transduced Sox6FLAG protein to the endogenous Sox6 promoter is accompanied, in erythroid cells, by strong downregulation of the endogenous Sox6 transcript and by decreased in vivo chromatin accessibility of this region to the PstI restriction enzyme. These observations suggest that the negative Sox6 autoregulation, mediated by the double Sox6 binding site within its own promoter, may be relevant to control the Sox6 transcriptional downregulation that we observe in human erythroid cultures and in mouse bone marrow cells in late erythroid maturation.
|Repression of E-cadherin by the polycomb group protein EZH2 in cancer.|
Cao, Q; Yu, J; Dhanasekaran, SM; Kim, JH; Mani, RS; Tomlins, SA; Mehra, R; Laxman, B; Cao, X; Yu, J; Kleer, CG; Varambally, S; Chinnaiyan, AM
Oncogene 27 7274-84 2008
Enhancer of zeste homolog 2 (EZH2) is a critical component of the polycomb-repressive complex 2 (PRC2), which is involved in gene silencing and histone H3 lysine 27 methylation. EZH2 has a master regulatory function in controlling such processes as stem cell differentiation, cell proliferation, early embryogenesis and X chromosome inactivation. Although benign epithelial cells express very low levels of EZH2, increased levels of EZH2 have been observed in aggressive solid tumors such as those of the prostate, breast and bladder. The mechanism by which EZH2 mediates tumor aggressiveness is unclear. Here, we demonstrate that EZH2 mediates transcriptional silencing of the tumor suppressor gene E-cadherin by trimethylation of H3 lysine 27. Histone deacetylase inhibitors can prevent EZH2-mediated repression of E-cadherin and attenuate cell invasion, suggesting a possible mechanism that may be useful for the development of therapeutic treatments. Taken together, these observations provide a novel mechanism of E-cadherin regulation and establish a functional link between dysregulation of EZH2 and repression of E-cadherin during cancer progression.
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