SAP30, a Novel Protein Conserved between Human and Yeast, Is a Component of a Histone Deacetylase Complex

Zhang, Yi; Sun, Zu‐Wen; Iratni, Rabah; Erdjument‐Bromage, Hediye; Tempst, Paul; Hampsey, Michael; Reinberg, Danny

doi:10.1016/s1097-2765(00)80102-1

Cited by 265 publications

(242 citation statements)

References 64 publications

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“…Hos3p and Sir2p are TSA-insensitive, Sir2p is activated by nicotinamide adenine dinucleotide (NAD), and little is known about Hos1p and Hos2p (5,6). Rpd3p forms a complex with Sin3p and Sap30p that is recruited to DNA by the Ume6p transcription factor (7,8). SIR2 is one of the silent information regulator (SIR) genes that mediate silencing (repression) at telomeres, mating type loci and ribosomal DNA (8,9).…”

Section: Biochemistry For the Article ''Functional Transitions In Mymentioning

confidence: 99%

Genomewide studies of histone deacetylase function in yeast

Bernstein

Tong²,

Schreiber³

2000

Proc. Natl. Acad. Sci. U.S.A.

393

310

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The trichostatin A (TSA)-sensitive histone deacetylase (HDAC) Rpd3p exists in a complex with Sin3p and Sap30p in yeast that is recruited to target promoters by transcription factors including Ume6p. Sir2p is a TSA-resistant HDAC that mediates yeast silencing. The transcription profile of rpd3 is similar to the profiles of sin3 , sap30 , ume6 , and TSA-treated wild-type yeast. A Ume6p-binding site was identified in the promoters of genes up-regulated in the sin3 strain. Two genes appear to participate in feedback loops that modulate HDAC activity: ZRT1 encodes a zinc transporter and is repressed by RPD3 (Rpd3p is zinc-dependent); BNA1 encodes a nicotinamide adenine dinucleotide (NAD)-biosynthesis enzyme and is repressed by SIR2 (Sir2p is NAD-dependent). Although HDACs are transcriptional repressors, deletion of RPD3 down-regulates certain genes. Many of these are down-regulated rapidly by TSA, indicating that Rpd3p may also activate transcription. Deletion of RPD3 previously has been shown to repress (“silence”) reporter genes inserted near telomeres. The profiles demonstrate that 40% of endogenous genes located within 20 kb of telomeres are down-regulated by RPD3 deletion. Rpd3p appears to activate telomeric genes sensitive to histone depletion indirectly by repressing transcription of histone genes. Rpd3p also appears to activate telomeric genes repressed by the silent information regulator (SIR) proteins directly, possibly by deacetylating lysine 12 of histone H4. Finally, bioinformatic analyses indicate that the yeast HDACs RPD3 , SIR2 , and HDA1 play distinct roles in regulating genes involved in cell cycle progression, amino acid biosynthesis, and carbohydrate transport and utilization, respectively.

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Section: Biochemistry For the Article ''Functional Transitions In Mymentioning

confidence: 99%

Genomewide studies of histone deacetylase function in yeast

Bernstein

Tong²,

Schreiber³

2000

Proc. Natl. Acad. Sci. U.S.A.

393

310

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“…Similarly, corepressors are apparent targets of signal transduction pathways, with activation of MAP kinase cascades correlating with a redistribution of SMRT from a predominantly nuclear location to a predominantly perinuclear or cytoplasmic compartment (69,70). The N terminus of N-CoR has been shown to interact with mSiah2, the mammalian homologue of Drosophila Seven in absentia (71), implicated in regulating proteosomal degradation of proteins. Based on cotransfection assays mSiah2 can mediate a dramatic decrease of N-CoR protein levels, blocked by a proteosome inhibitor.…”

Section: Coactivators and Corepressors As Targets Of Signalmentioning

confidence: 99%

Coregulator Codes of Transcriptional Regulation by Nuclear Receptors

Rosenfeld¹,

Glass²

2001

Journal of Biological Chemistry

467

371

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Members of the nuclear receptor superfamily directly activate or repress target genes by binding to hormone response elements (HREs) 1 in promoter or enhancer regions, and by binding to other DNA sequence-specific activators and can inhibit the transcriptional activities of other classes of transcription factors by transrepression. Hormone response elements provide specificity to receptor homodimer heterodimer binding (reviewed in Ref.2). Nuclear receptor functions are directed by specific activation domains, referred to as activation function 1 (AF-1), which resides in the N terminus, and activation function 2 (AF-2), which resides in the C-terminal ligand binding domain (LBD) (reviewed in Ref. 1). Regulation of gene transcription by nuclear receptors requires the recruitment of proteins characterized as coregulators, with liganddependent exchange of corepressors for coactivators serving as the basic mechanism for switching gene repression to activation. In this review, we discuss biochemical and genetic studies suggesting that coregulatory complexes are differentially utilized in both a cell-and promoter-specific fashion to activate or repress gene transcription. These coregulatory components, themselves targets of diverse intracellular signaling pathways, provide a combinatorial code for tissue-and gene-specific responses, utilizing both enzymatic and platform assembly functions to mediate the actions of nuclear receptor genetic programs critical for developmental and homeostatic processes in metazoan organisms. Nuclear Receptor CoactivatorsA diverse group of proteins have emerged as potential coactivators for nuclear receptors. Ligand-dependent recruitment of coactivators is dependent on AF-2, which consists of a short conserved helical sequence within the C terminus of the LBD (2). Biochemical and expression cloning approaches have been used to identify a large number of factors that interact with nuclear receptors in either a ligand-independent or a ligand-dependent manner and are often components of large multiprotein complexes. Many of these factors are capable of potentiating nuclear receptor activity in transient cotransfection assays. In addition, a distinct set of coactivators is associated with the AF-1 domain. As the number of potential coregulators clearly exceeds the capacity for direct interaction by a single receptor, the most plausible hypothesis is that transcriptional activation by nuclear receptors involves the actions of multiple factors. These factors act in a sequential and/or combinatorial manner to reorganize chromatin templates and to modify and recruit basal factors and RNA polymerase II (3, 4). ATP-dependent Chromatin Remodeling ComplexesAs chromatinized transcription units are "repressed" compared with naked DNA, a critical aspect of gene activation involves nucleosomal remodeling (reviewed in Refs. 3-5). Two general classes of chromatin remodeling factors that appear to play critical roles in transcriptional activation by nuclear receptors have been identified. These are ATP-depen...

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“…The HDACs confer enzymatic potential on the complex and the other proteins are presumed to regulate or target this activity. For example, the RbAps likely present HDACs 1 and 2 to their chromatin substrate (Parthun et al, 1996;Zhang et al, 1998). SAP18 and SAP30 appear to be important for interactions with selected transcriptional repressors and for HDAC activity in a subset of cellular HDAC1/2 complexes Espinas et al, 2000;Wang et al, 2002).…”

Section: Indirect Interactions With Hdacs-sin3 Complexmentioning

confidence: 99%

ETO interacting proteins

Hug

Lazar

2004

Oncogene

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The 8;21 translocation produces a fusion between the ETO gene and that encoding the myeloid transcription factor AML1. The AML1-ETO fusion substitutes the majority of the ETO protein for the coregulator recruitment domains of AML1. Biochemical analyses of ETO have led to the identification of numerous interacting proteins including many corepressors. Importantly, the proteins interacting with ETO are different from those of wild-type AML1, suggesting that altered coregulator recruitment underlies the oncogenic properties of AML1-ETO. The list of corepressors capable of binding ETO includes histone deacetylases (HDACs) and components of distinct HDAC core complexes. These investigations have provided mechanistic insight into corepressor recruitment by ETO and clues to the leukemogenic activity of AML1-ETO.

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SAP30, a Novel Protein Conserved between Human and Yeast, Is a Component of a Histone Deacetylase Complex

Cited by 265 publications

References 64 publications

Genomewide studies of histone deacetylase function in yeast

Genomewide studies of histone deacetylase function in yeast

Coregulator Codes of Transcriptional Regulation by Nuclear Receptors

ETO interacting proteins

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