Direct binding of TReP‐132 with TdT results in reduction of TdT activity

Fujisaki, Seiichiro; Sato, Ayumu; Toyomoto, T.; Hayano, Takahide; Sugai, Maki; Kubota, Takashi; Koiwai, Osamu

doi:10.1111/j.1365-2443.2005.00916.x

Cited by 12 publications

(26 citation statements)

References 36 publications

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“…Given that SAEG-1 and SAEG-2 are nuclear localized (Figure 2C and 2D), we wondered if EGL-4/PKG, SAEG-1 and SAEG-2 could physically interact with each other. Indeed, the mammalian orthologs of SAEG-1 and SAEG-2, TRERF1 and Dnttip1 respectively, have been shown to interact with each other in vitro [44]. We confirmed that SAEG-2 co-immunoprecipitated with itself and with SAEG-1, but not the yellow fluorescent protein Venus when over-expressed in Drosophila S2 cells (Figure 3A, lanes 3 and 4; Figure S4A, lanes 2 and 4).…”

Section: Resultssupporting

confidence: 64%

“…In cell culture systems, TRERF1 has been reported to activate CYP11A1, a gene required for steroidogenesis [41]. TRERF1 also interacts with Dnttip1 and together, they have been implicated in V(D)J recombination by antagonizing the terminal deoxynucleotidyltransferase (TdT) [44]. Another SAEG-1 ortholog, ZNF541, has been implicated in chromatin remodeling during spermatogenesis in mice [40].…”

Section: Discussionmentioning

confidence: 99%

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Nuclear cGMP-Dependent Kinase Regulates Gene Expression via Activity-Dependent Recruitment of a Conserved Histone Deacetylase Complex

Hao

Box

et al. 2011

PLoS Genet

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Elevation of the second messenger cGMP by nitric oxide (NO) activates the cGMP-dependent protein kinase PKG, which is key in regulating cardiovascular, intestinal, and neuronal functions in mammals. The NO-cGMP-PKG signaling pathway is also a major therapeutic target for cardiovascular and male reproductive diseases. Despite widespread effects of PKG activation, few molecular targets of PKG are known. We study how EGL-4, the Caenorhabditis elegans PKG ortholog, modulates foraging behavior and egg-laying and seeks the downstream effectors of EGL-4 activity. Using a combination of unbiased forward genetic screen and proteomic analysis, we have identified a conserved SAEG-1/SAEG-2/HDA-2 histone deacetylase complex that is specifically recruited by activated nuclear EGL-4. Gene expression profiling by microarrays revealed >40 genes that are sensitive to EGL-4 activity in a SAEG-1–dependent manner. We present evidence that EGL-4 controls egg laying via one of these genes, Y45F10C.2, which encodes a novel protein that is expressed exclusively in the uterine epithelium. Our results indicate that, in addition to cytoplasmic functions, active EGL-4/PKG acts in the nucleus via a conserved Class I histone deacetylase complex to regulate gene expression pertinent to behavioral and physiological responses to cGMP. We also identify transcriptional targets of EGL-4 that carry out discrete components of the physiological response.

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Section: Resultssupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Nuclear cGMP-Dependent Kinase Regulates Gene Expression via Activity-Dependent Recruitment of a Conserved Histone Deacetylase Complex

Hao

Box

et al. 2011

PLoS Genet

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“…TdT contributes to the diversity of immunoglobulins and T-cell receptors in lymphocytes [2], [3]. TdIF1 negatively regulates TdT activity [1], [4], [5] and controls TdT degradation through the Bood POZ-containing gene type-2 (BPOZ-2)-mediated ubiquitin proteasome system [6], [7]. These previous studies showed that TdIF1 controls TdT in lymphocytes at the post-translational level.…”

Section: Introductionmentioning

confidence: 93%

“…Several lines of evidence implicate TdIF1 in controlling transcription. Human TdIF1 is reported to bind to TReP-132 (also known as TRERF1), a transcriptional co-activator of steroidogenic factor 1, which induces p450scc gene expression in steroid-hormone-producing cells [4], [9]. In addition, in M-phase cells human TdIF1 associates with histone deacetylases HDAC1 and HDAC2 in a multisubunit complex [10], that may act in transcriptional regulation.…”

Section: Introductionmentioning

confidence: 99%

TdIF1 Recognizes a Specific DNA Sequence through Its Helix-Turn-Helix and AT-Hook Motifs to Regulate Gene Transcription

et al. 2013

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TdIF1 was originally identified as a protein that directly binds to DNA polymerase TdT. TdIF1 is also thought to function in transcription regulation, because it binds directly to the transcriptional factor TReP-132, and to histone deacetylases HDAC1 and HDAC2. Here we show that TdIF1 recognizes a specific DNA sequence and regulates gene transcription. By constructing TdIF1 mutants, we identify amino acid residues essential for its interaction with DNA. An in vitro DNA selection assay, SELEX, reveals that TdIF1 preferentially binds to the sequence 5′-GNTGCATG-3′ following an AT-tract, through its Helix-Turn-Helix and AT-hook motifs. We show that four repeats of this recognition sequence allow TdIF1 to regulate gene transcription in a plasmid-based luciferase reporter assay. We demonstrate that TdIF1 associates with the RAB20 promoter, and RAB20 gene transcription is reduced in TdIF1-knocked-down cells, suggesting that TdIF1 stimulates RAB20 gene transcription.

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“…It is currently unclear if the ability to randomly bind substrates plays a physiological role in generating random nucleotides during recombination. However, it is possible that the interactions of TdT with PCNA and Ku70/86 [107–109], proteins involved in replication and recombination, may influence its kinetic mechanism.…”

Section: Mechanism Of Template-independent Polymerizationmentioning

confidence: 99%

Terminal deoxynucleotidyl transferase: The story of a misguided DNA polymerase

Motea

Berdis

2010

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

211

179

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Nearly every DNA polymerase characterized to date exclusively catalyzes the incorporation of mononucleotides into a growing primer using a DNA or RNA template as a guide to direct each incorporation event. There is, however, one unique DNA polymerase designated terminal deoxynucleotidyl transferase that performs DNA synthesis using only single-stranded DNA as the nucleic acid substrate. In this chapter, we review the biological role of this enigmatic DNA polymerase and the biochemical mechanism for its ability to perform DNA synthesis in the absence of a templating strand. We compare and contrast the molecular events for template-independent DNA synthesis catalyzed by terminal deoxynucleotidyl transferase with other well-characterized DNA polymerases that perform template-dependent synthesis. This includes a quantitative inspection of how terminal deoxynucleotidyl transferase binds DNA and dNTP substrates, the possible involvement of a conformational change that precedes phosphoryl transfer, and kinetic steps that are associated with the release of products. These enzymatic steps are discussed within the context of the available structures of terminal deoxynucleotidyl transferase in the presence of DNA or nucleotide substrate. In addition, we discuss the ability of proteins involved in replication and recombination to regulate the activity of the terminal deoxynucleotidyl transferase. Finally, the biomedical role of this specialized DNA polymerase is discussed focusing on its involvement in cancer development and its use in biomedical applications such as labeling DNA for detecting apoptosis.

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Direct binding of TReP‐132 with TdT results in reduction of TdT activity

Cited by 12 publications

References 36 publications

Nuclear cGMP-Dependent Kinase Regulates Gene Expression via Activity-Dependent Recruitment of a Conserved Histone Deacetylase Complex

Nuclear cGMP-Dependent Kinase Regulates Gene Expression via Activity-Dependent Recruitment of a Conserved Histone Deacetylase Complex

TdIF1 Recognizes a Specific DNA Sequence through Its Helix-Turn-Helix and AT-Hook Motifs to Regulate Gene Transcription

Terminal deoxynucleotidyl transferase: The story of a misguided DNA polymerase

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