Retinoblastoma protein tethered to promoter DNA represses TBP-mediated transcription

Luca, Pasquale De; Majello, Barbara; Lania, Luigi

doi:10.1002/(sici)1097-4644(19980801)70:2<281::aid-jcb13>3.0.co;2-q

Cited by 17 publications

(9 citation statements)

References 27 publications

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“…Recent data indicate that the Rb-associated histone deacetylase complex is involved in transcriptional repression of E2F responsive genes (29,30,31,32,(33)(34)(35). Our results (Fig.…”

Section: Discussionsupporting

confidence: 57%

RbAp48 Belongs to the Histone Deacetylase Complex That Associates with the Retinoblastoma Protein

Nicolas¹,

Morales²,

Magnaghi-Jaulin³

et al. 2000

Journal of Biological Chemistry

118

100

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The retinoblastoma susceptibility gene product, the Rb protein, is a key regulator of mammalian cell proliferation. One of the major targets of Rb is the S phase inducing E2F transcription factor. Once bound to E2F, Rb represses the expression of E2F-regulated genes. Transcriptional repression by Rb is believed to be crucial for the proper control of cell growth. Recently, we and others showed that Rb represses transcription through the recruitment of a histone deacetylase. Interestingly, we show here that the Rb-associated histone deacetylase complex could deacetylate polynucleosomal substrates, indicating that other proteins could be present within this complex. The Rb-associated protein RbAp48 belongs to many histone deacetylase complexes. We show here that the histone deacetylase HDAC1 is able to mediate the formation of a ternary complex containing Rb and RbAp48. Moreover, less deacetylase activity was found associated with Rb in cell extracts depleted for RbAp48 containing complexes, demonstrating that Rb, histone deacetylase, and RbAp48 are physically associated in live cells. Taken together, these data indicate that RbAp48 is a component of the histone deacetylase complex recruited by Rb. Finally, we found that E2F1 and RbAp48 are physically associated in the presence of Rb and HDAC1, suggesting that RbAp48 could be involved in transcriptional repression of E2F-responsive genes.

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“…Recent data indicate that the Rb-associated histone deacetylase complex is involved in transcriptional repression of E2F responsive genes (29,30,31,32,(33)(34)(35). Our results (Fig.…”

Section: Discussionsupporting

confidence: 57%

RbAp48 Belongs to the Histone Deacetylase Complex That Associates with the Retinoblastoma Protein

Nicolas¹,

Morales²,

Magnaghi-Jaulin³

et al. 2000

Journal of Biological Chemistry

118

100

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“…Sp3 is a ubiquitously expressed transcription factor, closely related to Sp1 but, unlike Sp1, often functioning as a transcriptional repressor by means of interacting with GC-rich Sp1-like sites (31,32). It has also been shown that Sp3 acts as a bi-functional regulator whose activating or repressing activity is dependent upon both the promoter and the cellular context (27,33).…”

Section: Our Results Show That Tieg2 Was An Activator For the Human Mmentioning

confidence: 99%

Dual Functions of Transcription Factors, Transforming Growth Factor-β-inducible Early Gene (TIEG)2 and Sp3, Are Mediated by CACCC Element and Sp1 Sites of Human Monoamine Oxidase (MAO) B Gene

Chen

Shih

2004

Journal of Biological Chemistry

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Monoamine oxidases (MAO)A and B catalyze the oxidative deamination of many biogenic and dietary amines. Abnormal expression of MAO has been implicated in several psychiatric and neurodegenerative disorders. Human MAO B core promoter (؊246 to ؊99 region) consists of CACCC element flanked by two clusters of overlapping Sp1 sites. Here, we show that cotransfection with transforming growth factor (TGF)-␤-inducible early gene (TIEG)2 increased MAO B gene expression at promoter, mRNA, protein, and catalytic activity levels in both SH-SY5Y and HepG2 cells. Mutation of the CACCC element increased the MAO B promoter activity, and cotransfection with TIEG2 further increased the promoter activity, suggesting that CACCC was a repressor element. This increase was reduced when the proximal Sp1 overlapping sites was mutated. Similar interactions were found with Sp3. These results showed that TIEG2 and Sp3 were repressors at the CACCC element but were activators at proximal Sp1 overlapping sites of MAO B. Gel-shift and chromatin immunoprecipitation assays showed that TIEG2 and Sp3 bound directly to CACCC element and the proximal Sp1 sites in both synthetic oligonucleotides and natural MAO B core promoter. TIEG2 had a higher affinity to Sp1 sites than CACCC element, whereas Sp3 had an equal affinity to both elements. Thus, TIEG2 was an activator, but Sp3 had no effect on MAO B gene expression. This study provides new insights into MAO B gene expression and illustrates the complexity of gene regulation.Monoamine oxidase (MAO) 1 plays an important role in the metabolism of biogenic amines, including serotonin (5-hydroxytryptamine), norepinephrine, dopamine, tyramine, and phenylethylamine (PEA). There are two isoenzymes of MAO (MAO A and MAO B) that exhibit distinct substrate and inhibitor specificity (1, 2; for review, see Ref.3). Although both forms of MAO are expressed throughout the body, they differ in celland tissue-specific expressions. Placenta and fibroblasts predominantly express MAO A (4, 5), and platelets and lymphocytes express only MAO B (6). In the brain, even though MAO A prefers 5-hydroxytryptamine and MAO B prefers PEA as substrate, MAO B but not MAO A was found in serotonergic neurons (7,8). MAO A was expressed in catecholaminergic neurons, whereas MAO B is rich in astrocytes. Moreover, MAO B but not MAO A activity increases progressively in the brain throughout adult life (7, 9).MAO A and MAO B are coded by different genes (10) and are closely linked on X chromosome, Xp11.2-11.4 (11). Both consist of 15 exons with identical exon-intron organization (12). The promoter of MAO A has bi-directional activity (13) and consists of a functional polymorphism in a 30-bp repeat sequence (14). The 5Ј-flanking sequence of MAO B gene has been characterized. The maximal promoter activity for MAO B gene was found to be in the Ϫ246 to Ϫ99 region. This region consists of two clusters of overlapping Sp1 sites separated by a CACCC element (15). Previously, we have shown that Sp1 and Sp3 can bind to both proximal and distal clusters...

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“…The involvement of the DRE–DREF system in TBP gene expression suggests that the expression of TBP is also related to cell division and cell proliferation. In addition, TBP is known to be a major target for the regulation of the expression of genes related to cell proliferation, because of its interaction with transcription factors such as retinoblastoma (RB) protein [30], p53 [31,32], E1A [33], c‐Myc [34], and v‐Myb [35]. For these reasons we believe that the regulation of TBP gene expression is likely to be important for cell division and/or proliferation.…”

Section: Discussionmentioning

confidence: 99%

The DNA replication‐related element (DRE)–DRE‐binding factor (DREF) system may be involved in the expression of theDrosophila melanogaster TBPgene

Choi

Cho

et al. 2000

FEBS Letters

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The TATA box binding protein (TBP) is a general transcription factor required for initiation by all three eukaryotic RNA polymerases. Previously, we found that the promoter region of the Drosophila melanogaster TBP gene contains three sequences similar to the DNA replication-related element (DRE) (5P P-TATCGATA). In the present study, we found that the DRElike sequences are also present in the promoter of the Drosophila virilis TBP gene, suggesting a role for these sequences in TBP expression. Band mobility shift assays revealed that oligonucleotides containing sequences similar to the DRE of D. melanogaster TBP gene promoter form specific complexes with a factor in a Kc cell nuclear extract and with recombinant DRE-binding factor (DREF). Furthermore, these complexes were either supershifted or diminished by monoclonal antibodies to DREF. Transient luciferase assays demonstrated that induction of mutations in two DRE-related sequences at positions 3 3223 and 3 363 resulted in an extensive reduction of promoter activity. Thus, the DRE^DREF system appears to be involved in the expression of the D. melanogaster TBP gene. ß

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Retinoblastoma protein tethered to promoter DNA represses TBP-mediated transcription

Cited by 17 publications

References 27 publications

RbAp48 Belongs to the Histone Deacetylase Complex That Associates with the Retinoblastoma Protein

RbAp48 Belongs to the Histone Deacetylase Complex That Associates with the Retinoblastoma Protein

Dual Functions of Transcription Factors, Transforming Growth Factor-β-inducible Early Gene (TIEG)2 and Sp3, Are Mediated by CACCC Element and Sp1 Sites of Human Monoamine Oxidase (MAO) B Gene

The DNA replication‐related element (DRE)–DRE‐binding factor (DREF) system may be involved in the expression of theDrosophila melanogaster TBPgene

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