scholarly journals Functional Divergence between Histone Deacetylases in Fission Yeast by Distinct Cellular Localization and In Vivo Specificity

2002 ◽  
Vol 22 (7) ◽  
pp. 2170-2181 ◽  
Author(s):  
Pernilla Bjerling ◽  
Rebecca A. Silverstein ◽  
Geneviève Thon ◽  
Amy Caudy ◽  
Shiv Grewal ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Cellular Localization ◽  
Functional Divergence ◽  
Binding Pocket ◽  
Class Ii ◽  
Class I ◽  
Chromosome Loss ◽  
Level Of Activity ◽  
High Level

ABSTRACT Histone deacetylases (HDACs) are important for gene regulation and the maintenance of heterochromatin in eukaryotes. Schizosaccharomyces pombe was used as a model system to investigate the functional divergence within this conserved enzyme family. S. pombe has three HDACs encoded by the hda1+ , clr3+ , and clr6+ genes. Strains mutated in these genes have previously been shown to display strikingly different phenotypes when assayed for viability, chromosome loss, and silencing. Here, conserved differences in the substrate binding pocket identify Clr6 and Hda1 as class I HDACs, while Clr3 belongs in the class II family. Furthermore, these HDACs were shown to have strikingly different subcellular localization patterns. Hda1 was localized to the cytoplasm, while most of Clr3 resided throughout the nucleus. Finally, Clr6 was localized exclusively on the chromosomes in a spotted pattern. Interestingly, Clr3, the only HDAC present in the nucleolus, was required for ribosomal DNA (rDNA) silencing. Clr3 presumably acts directly on heterochromatin, since it colocalized with the centromere, mating-type region, and rDNA as visualized by in situ hybridization. In addition, Clr3 could be cross-linked to mat3 in chromatin immunoprecipitation experiments. Western analysis of bulk histone preparations indicated that Hda1 (class I) had a generally low level of activity in vivo and Clr6 (class I) had a high level of activity and broad in vivo substrate specificity, whereas Clr3 (class II) displayed its main activity on acetylated lysine 14 of histone H3. Thus, the distinct functions of the S. pombe HDACs are likely explained by their distinct cellular localization and their different in vivo specificities.

scholarly journals Inhibition of Polyomavirus ori-Dependent DNA Replication by mSin3B

2002 ◽  
Vol 76 (23) ◽  
pp. 11809-11818 ◽  
Author(s):  
An-Yong Xie ◽  
William R. Folk
Keyword(s):  
Dna Replication ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Class Ii ◽  
T Antigen ◽  
Class I ◽  
Large T Antigen ◽  
Transcriptional Corepressor ◽  
Independent Mechanism

ABSTRACT When tethered in cis to DNA, the transcriptional corepressor mSin3B inhibits polyomavirus (Py) ori-dependent DNA replication in vivo. Histone deacetylases (HDACs) appear not to be involved, since tethering class I and class II HDACs in cis does not inhibit replication and treating the cells with trichostatin A does not specifically relieve inhibition by mSin3B. However, the mSin3B L59P mutation that impairs mSin3B interaction with N-CoR/SMRT abrogates inhibition of replication, suggesting the involvement of N-CoR/SMRT. Py large T antigen interacts with mSin3B, suggesting an HDAC-independent mechanism by which mSin3B inhibits DNA replication.

scholarly journals HDACs class II-selective inhibition alters nuclear receptor-dependent differentiation

2010 ◽  
Vol 45 (4) ◽  
pp. 219-228 ◽  
Author(s):  
Angela Nebbioso ◽  
Carmela Dell'Aversana ◽  
Anne Bugge ◽  
Roberta Sarno ◽  
Sergio Valente ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Selective Inhibition ◽  
Class Ii ◽  
Class I ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
F9 Cells ◽  
Anti Cancer ◽  
Cardiovascular Defects

Epigenetic deregulation contributes to diseases including cancer, neurodegeneration, osteodystrophy, cardiovascular defects, and obesity. For this reason, several inhibitors for histone deacetylases (HDACs) are being validated as novel anti-cancer drugs in clinical studies and display important anti-proliferative activities. While most inhibitors act on both class I, II, and IV HDACs, evidence is accumulating that class I is directly involved in regulation of cell growth and death, whereas class II members regulate differentiation processes, such as muscle and neuronal differentiation. Here, we show that the novel class II-selective inhibitor MC1568 interferes with the RAR- and peroxisome proliferator-activated receptor γ (PPARγ)-mediated differentiation-inducing signaling pathways. In F9 cells, this inhibitor specifically blocks endodermal differentiation despite not affecting retinoic acid-induced maturation of promyelocytic NB4 cells. In 3T3-L1 cells, MC1568 attenuates PPARγ-induced adipogenesis, while the class I-selective MS275 blocked adipogenesis completely thus revealing a different mode of action and/or target profile of the two classes of HDACs. Using in vivo reporting PPRE-Luc mice, we find that MC1568 impairs PPARγ signaling mostly in the heart and adipose tissues. These results illustrate how HDAC functions can be dissected by selective inhibitors.

scholarly journals Isolation of a novel histone deacetylase reveals that class I and class II deacetylases promote SMRT-mediated repression

2000 ◽  
Vol 14 (1) ◽  
pp. 55-66 ◽  
Author(s):  
Hung-Ying Kao ◽  
Michael Downes ◽  
Peter Ordentlich ◽  
Ronald M. Evans
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylases ◽  
Mammalian Cells ◽  
Class Ii ◽  
Class I ◽  
Nuclear Compartment ◽  
New Family ◽  
Repressive Effect ◽  
Two Hybrid

The transcriptional corepressor SMRT functions by mediating the repressive effect of transcription factors involved in diverse signaling pathways. The mechanism by which SMRT represses basal transcription has been proposed to involve the indirect recruitment of histone deacetylase HDAC1 via the adaptor mSin3A. In contrast to this model, a two-hybrid screen on SMRT-interacting proteins resulted in the isolation of the recently described HDAC5 and a new family member termed HDAC7. Molecular and biochemical results indicate that this interaction is direct and in vivo evidence colocalizes SMRT, mHDAC5, and mHDAC7 to a distinct nuclear compartment. Surprisingly, HDAC7 can interact with mSin3A in yeast and in mammalian cells, suggesting association of multiple repression complexes. Taken together, our results provide the first evidence that SMRT-mediated repression is promoted by class I and class II histone deacetylases and that SMRT can recruit class II histone deacetylases in a mSin3A-independent fashion.

scholarly journals Functional Divergence between Histone Deacetylases in Fission Yeast by Distinct Cellular Localization and In Vivo Specificity

2002 ◽  
Vol 22 (14) ◽  
pp. 5257-5258
Author(s):  
Pernilla Bjerling ◽  
Rebecca A. Silverstein ◽  
Geneviève Thon ◽  
Amy Caudy ◽  
Shiv Grewal ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Histone Deacetylases ◽  
Cellular Localization ◽  
Functional Divergence

Inhibition of both class I and class II histone deacetylases is required to effectively inhibit osteoclast bone resorption in vivo and in vitro

Bone ◽  
2009 ◽  
Vol 44 ◽  
pp. S133-S134
Author(s):  
M.D. Cantley ◽  
D.P. Fairlie ◽  
M.P. Bartold ◽  
K.D. Rainsford ◽  
D.R. Haynes
Keyword(s):  
Bone Resorption ◽  
Histone Deacetylases ◽  
Class Ii ◽  
Class I

A rapid and reliable in vivo method for anti-GPLA (class I and class II antigens) antibody titration and GPLA typing

1983 ◽  
Vol 59 (2) ◽  
pp. 205-215 ◽  
Author(s):  
Thérèse Neveu ◽  
Michèle Lefroit-Joliy ◽  
Guy André Voisin
Keyword(s):  
Class Ii ◽  
Class I ◽  
Class Ii Antigens

scholarly journals Functional Interaction between Class II Histone Deacetylases and ICP0 of Herpes Simplex Virus Type 1

2004 ◽  
Vol 78 (13) ◽  
pp. 6744-6757 ◽  
Author(s):  
Patrick Lomonte ◽  
Joëlle Thomas ◽  
Pascale Texier ◽  
Cécile Caron ◽  
Saadi Khochbin ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Histone Deacetylases ◽  
Class Ii ◽  
Class I ◽  
Transfected Cells ◽  
Amino Terminal ◽  
Simplex Virus ◽  
Class I Hdacs

ABSTRACT This study describes the physical and functional interactions between ICP0 of herpes simplex virus type 1 and class II histone deacetylases (HDACs) 4, 5, and 7. Class II HDACs are mainly known for their participation in the control of cell differentiation through the regulation of the activity of the transcription factor MEF2 (myocyte enhancer factor 2), implicated in muscle development and neuronal survival. Immunofluorescence experiments performed on transfected cells showed that ICP0 colocalizes with and reorganizes the nuclear distribution of ectopically expressed class I and II HDACs. In addition, endogenous HDAC4 and at least one of its binding partners, the corepressor protein SMRT (for silencing mediator of retinoid and thyroid receptor), undergo changes in their nuclear distribution in ICP0-transfected cells. As a result, during infection endogenous HDAC4 colocalizes with ICP0. Coimmunoprecipitation and glutathione S-transferase pull-down assays confirmed that class II but not class I HDACs specifically interacted with ICP0 through their amino-terminal regions. This region, which is not conserved in class I HDACs but homologous to the MITR (MEF2-interacting transcription repressor) protein, is responsible for the repression, in a deacetylase-independent manner, of MEF2 by sequestering it under an inactive form in the nucleus. Consequently, we show that ICP0 is able to overcome the HDAC5 amino-terminal- and MITR-induced MEF2A repression in gene reporter assays. This is the first report of a viral protein interacting with and controlling the repressor activity of class II HDACs. We discuss the putative consequences of such an interaction for the biology of the virus both during lytic infection and reactivation from latency.

scholarly journals Widespread and selective induction of major histocompatibility complex-determined antigens in vivo by gamma interferon.

1985 ◽  
Vol 162 (5) ◽  
pp. 1645-1664 ◽  
Author(s):  
M J Skoskiewicz ◽  
R B Colvin ◽  
E E Schneeberger ◽  
P S Russell
Keyword(s):  
Dendritic Cells ◽  
Small Intestine ◽  
Antigen Expression ◽  
Class Ii ◽  
Gamma Interferon ◽  
The Body ◽  
Class I ◽  
Ifn Gamma ◽  
Histocompatibility Complex

gamma Interferon (IFN-gamma) caused remarkable increases in class I (H-2Kk) and class II (I-Ak) antigens throughout the body by 6-9 d. Heart, kidney, and adrenals showed increases of 4-8 times their previous levels of class I antigen content, while the pancreas and small intestine increased 13-17-fold. Lesser increases were found in spleen, liver, and lung, which showed higher resting antigenic potency. Increases of class II antigenicity of 6-10-fold were found in heart, kidney, pancreas, lung, liver, adrenal, and small intestine, with lesser increases in thymus and spleen, and none in lymph node. Topographical analysis revealed that IFN-gamma induced class I and II antigens on most tissues in a highly selective fashion. For example, the renal proximal tubules expressed large amounts of both class I and II antigens, whereas the distal tubules and collecting ducts did not. In some epithelial cells class I and II determinants were induced only on the basal aspects of the cell membrane. IFN-gamma caused a remarkable increase in class II-positive dendritic cells in the liver, pancreas, salivary glands, and thyroid. Whether these cells were of local or systemic origin is uncertain, but the finding of a simultaneous depletion of dendritic cells from lymph nodes and spleen raises the possibility that they may have been derived, at least in part, from these sites. The dynamic and selective induction of class I and II antigen expression by IFN-gamma is likely to be important in regulation of the immune response in tissues.

Inhibitors of histone deacetylases in class I and class II suppress human osteoclasts in vitro

2011 ◽  
Vol 226 (12) ◽  
pp. 3233-3241 ◽  
Author(s):  
M.D. Cantley ◽  
D.P. Fairlie ◽  
P.M. Bartold ◽  
K.D. Rainsford ◽  
G.T. Le ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Class Ii ◽  
Class I ◽  
Human Osteoclasts
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