The Delta–Notch signal transduction pathway has widespread roles in animal development which it appears to control cell fate. CBF1/RBP-Jκ, the mammalian homolog of Drosophila Suppressor Hairless [Su(H)], switches from a transcriptional repressor an activator upon Notch activation. mechanism whereby regulates this switch is not clear. In report we show that prior induction CBF1/RBP-Jκ interacts with corepressor complex containing SMRT ( s ilencing m ediator r etinoid and t hyroid hormone...

Laszlo Nagy, Hung-Ying Kao, James D. Love, Chuan Li, Ester Banayo, John T. Gooch, V. Krishna, K. Chatterjee, Ronald M. Evans, and W.R. Schwabe Medical Research Council (MRC), Laboratory of Molecular Biology, Cambridge, CB2 2QH, UK; Howard Hughes Institute (HHMI), The Salk for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037 USA; Department Medicine, University Addenbrooke's Hospital, 2QQ, UK

The transcriptional corepressor SMRT functions by mediating the repressive effect of transcription factors involved in diverse signaling pathways. mechanism which represses basal has been proposed to involve indirect recruitment histone deacetylase HDAC1 via adaptor mSin3A. In contrast this model, a two-hybrid screen on SMRT-interacting proteins resulted isolation recently described HDAC5 and new family member termed HDAC7. Molecular biochemical results indicate that interaction is direct...

Degradation of a DNA methyltransferase implicated in cancer is determined by its acetylation status.

Nucleosomal histone modification is believed to be a critical step in the activation of RNA polymerase II-dependent transcription. p300/CBP and PCAF acetyltransferases (HATs) are coactivators for several transcription factors, including nuclear hormone receptors, p53, Stat1alpha, participate by forming an complex promoting acetylation. The adenoviral E1A oncoprotein represses transcriptional signaling binding displacing p/CIP proteins from complex. Here, we show that directly HAT activity...

A yeast two-hybrid screen using the conserved carboxyl terminus of nuclear receptor corepressor SMRT as a bait led to isolation novel human gene termed SHARP (SMRT/HDAC1 Associated Repressor Protein). is potent transcriptional repressor whose repression domain (RD) interacts directly with and at least five members NuRD complex including HDAC1 HDAC2. In addition, binds steroid RNA coactivator SRA via an intrinsic binding suppresses SRA-potentiated transcription activity. Accordingly, has...

Here we show that HDAC7, a member of the class II histone deacetylases, specifically targets several members myocyte enhancer factors, MEF2A, -2C, and -2D, inhibits their transcriptional activity. Furthermore, demonstrate DNA-bound MEF2C is capable recruiting demonstrating HDAC7-dependent repression transcription not due to inhibition MEF2 DNA binding The data also suggest promoter bound potentially remodeling adjacent nucleosomes via recruitment HDAC7. We have observed nucleocytoplasmic...

Histone acetylation was significantly increased in retinas from diabetic rats, and this inhibited diabetics treated with minocycline, a drug known to inhibit early retinopathy animals. expression of inflammatory proteins that have been implicated the pathogenesis were likewise cultured retinal Müller glia grown diabetes-like concentration glucose. Both induction elevated glucose levels by inhibitors histone acetyltransferase (garcinol antisense against acetylase, p300) or activators...

The oestrogen receptor (ER or ERα), a nuclear hormone that drives most breast cancer1, is commonly activated by phosphorylation at serine 118 within its intrinsically disordered N-terminal transactivation domain2,3. Although this modification enables oestrogen-independent ER function, mechanism has remained unclear despite ongoing clinical trials of kinase inhibitors targeting region4–6. By integration small-angle X-ray scattering and magnetic resonance spectroscopy with functional studies,...

Homeobox (hox) proteins have been shown to regulate cell fate and segment identity by promoting the expression of specific genetic programs.In contrast their restricted biological action in vivo, however, most homeodomain factors exhibit promiscuous DNA binding properties vitro, suggesting a requirement for additional cofactors that enhance target site selectivity.In this regard, pbx family homeobox genes has found heterodimerize with thereby augment activity certain hox on subset potential...

Here, we describe the identification and characterization of a nuclear body (matrix-associated deacetylase body) whose formation integrity depend on activity. Typically, there are 20–40 0.5-μM bodies per nucleus, although size number can vary substantially. The structure appears to contain both class I recently described II histone deacetylases (HDAC)5 7 along with receptor corepressors SMRT (silencing mediator for retinoid thyroid receptor) N-CoR (nuclear corepressor). Addition inhibitors...

Ataxin 1 (Atx1) is a foci-forming polyglutamine protein of unknown function, whose mutant form causes type spinocerebellar ataxia in humans and exerts neurotoxicity transgenic mouse fly expressing Atx1. In this study, we demonstrate that Atx1 interacts with the transcriptional corepressor SMRT (silencing mediator retinoid thyroid hormone receptors) histone deacetylase 3. binds chromosomes mediates repression when tethered to DNA. Interaction SMRT-related factors conserved feature Atx1,...

Today’s biomedical research has become heavily dependent on access to the biological knowledge encoded in expert curated databases. As volume of literature grows rapidly, it becomes increasingly difficult for biocurators keep up with because manual curation is an expensive and time-consuming endeavour. Past suggested that computer-assisted can improve efficiency, but few text-mining systems have been formally evaluated this regard. Through participation interactive track BioCreative 2012...

Alpha actinins (ACTNs) are known for their ability to modulate cytoskeletal organization and cell motility by cross-linking actin filaments. We show here that ACTN4 harbors a functional LXXLL receptor interaction motif, interacts with nuclear receptors in vitro mammalian cells, potently activates transcription mediated receptors. Whereas overexpression of potentiates estrogen α (ERα)-mediated transient transfection reporter assays, knockdown decreases it. In contrast, histone deacetylase 7...

Tip60 (Tat-interactiveprotein, 60 kDa), a cellular protein with intrinsic histone acetyltransferase activity, is involved in DNA damage repair and apoptosis. Recent studies have suggested that acts either as co-activator or co-repressor to modulate transcription. In this study, we demonstrate represses reporter gene expression when it fused the Gal4 binding domain. We also show associates deacetylase 7 (HDAC7) through its N-terminal zinc finger-containing region HDAC7 activity required for...

We have used suppressor genetics to identify factors that interact with Saccharomyces cerevisiae U1 small nuclear RNA (snRNA). In this way, we isolated PRP40-1, a restores growth at 18 degrees C strain bearing cold-sensitive mutation in RNA. A gene disruption experiment shows PRP40 is an essential gene. To study the role of splicing, created pool temperature-sensitive prp40 strains. Primer extension analysis intron-containing transcripts strains reveals splicing defect, indicating Prp40...

Histone acetylation/deacetylation plays an important role in the control of gene expression, tissue growth, and development. In particular, histone deacetylases 7 (HDAC7), a member class IIa HDACs, is crucial maintaining vascular integrity. However, whether HDAC7 involved processes endothelial signaling angiogenesis remains unclear. Here, we investigated growth factor (VEGF) angiogenesis.We show for first time that VEGF stimulated phosphorylation at sites Ser178, Ser344, Ser479 dose-...

Promyelocytic leukemia protein (PML) is an important regulator due to its role in numerous cellular processes including apoptosis, viral infection, senescence, DNA damage repair, and cell cycle regulation. Despite the of PML many functions, little known about regulation itself. We show that stability regulated through interaction with peptidyl-prolyl cis-trans isomerase Pin1. This mediated four serine-proline motifs C terminus PML. Binding Pin1 results degradation a phosphorylation-dependent...