Human CART1, a Paired-Class Homeodomain Protein, Activates Transcription through Palindromic Binding Sites

Cai, Richard

doi:10.1006/bbrc.1998.9257

Cited by 21 publications

(15 citation statements)

References 15 publications

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“…Interestingly, the motif that we identified resembles the one characterized for the homeodomain protein Cart-1, which is expressed in tissues undergoing chondrogenesis (29). The Cart-1 binding motif consists of two inverted TAAT sequences separated by three or four nucleotides (2). Computer searches for the identified Meox1 binding motif in the available genomic databases may help to identify additional target genes.…”

Section: Meox1 Directly Binds Thementioning

confidence: 76%

Meox Homeodomain Proteins Are Required forBapx1Expression in the Sclerotome and Activate Its Transcription by Direct Binding to Its Promoter

Rodrigo

Bovolenta

Mankoo

et al. 2004

Molecular and Cellular Biology

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The axial skeleton of vertebrates derives from the sclerotomal compartment of the somites. Genetic analysis has demonstrated that the transcription factors Pax1, Pax9, Meox1, Meox2, and Bapx1 are all required for sclerotomal differentiation. Their hierarchical relationship is, however, poorly understood. Because Bapx1 expression in the somites starts slightly later than that of the Meox genes, we asked whether Bapx1 is one of their downstream targets. Our analysis of Meox1; Meox2 mutant mice supports this hypothesis, as Bapx1 expression in the sclerotome is lost in the absence of both Meox proteins. Using transient-transfection assays, we show that Meox1 activates the Bapx1 promoter in a dose-dependent manner and that this activity is enhanced in the presence of Pax1 and/or Pax9. Furthermore, by electrophoretic mobility shift and chromatin immunoprecipitation experiments, we demonstrate that Meox1 can bind the Bapx1 promoter. The palindromic sequence TAATTA, present in the Bapx1 promoter, binds the Meox1 protein in vitro and is necessary for Meox1-induced transactivation of the Bapx1 promoter. Our data demonstrate that the Meox genes are required for Bapx1 expression in the sclerotome and suggest that the mechanism by which the Meox proteins exert this function is through direct activation of the Bapx1 gene.

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Section: Meox1 Directly Binds Thementioning

confidence: 76%

Meox Homeodomain Proteins Are Required forBapx1Expression in the Sclerotome and Activate Its Transcription by Direct Binding to Its Promoter

Rodrigo

Bovolenta

Mankoo

et al. 2004

Molecular and Cellular Biology

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“…ALX1 encodes for CART1, a paired-class homeodomain protein that is necessary for survival of the forebrain mesenchyme in rodents (36). While the binding site preferences for CART1 have been characterized, (37) the function of this protein in humans is not known. Although the precise role for CART1 in the antiviral response is not yet clear, a gene ontology analysis of ALX1 predicted targets suggests that this factor is functionally similar to STAT1 and FOXO3 (Figure 6).…”

Section: Discussionmentioning

confidence: 99%

Antiviral Response Dictated by Choreographed Cascade of Transcription Factors

Zaslavsky¹,

Hershberg

Seto³

et al. 2010

The Journal of Immunology

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, triggers a transcriptional program that includes the production of type I IFNs. These antiviral cytokines signal in both autocrine and paracrine fashion through the JAK-STAT pathway leading to additional transcription events involving the differential expression of many hundreds of genes. The antiviral state produced by this extensive genetic reprogramming involves a core set of genes as well as pathogenspecific components (1).The DC response to individual pathogens involves multiple signals that must be integrated to initiate an appropriate immune response. Pathogenic viruses attempt to subvert normal immune function through the expression of IFN antagonists (2, 3). For example, IFN regulatory factor (IRF) 3 activation and IFN-b expression are blocked by the NS1 protein of influenza (4). Unraveling the impact of these immune antagonists would be aided by a detailed understanding of the genetic regulatory network that operates during an uninhibited antiviral response. This knowledge is lacking because previous human studies have used viruses that interfere with the immune response (4-6). One fundamental unresolved question is to what extent the antiviral response is a single interconnected transcriptional cascade (convergent architecture) or a combination of transcriptional events operating independently in reaction to the multiple signals that arise following viral insult (parallel architecture). Newcastle disease virus (NDV) infection of human DCs provides an ideal system to define the uninhibited regulatory network (7,8). NDV is an avian virus that is able to stimulate innate immunity and DC maturation, but lacks the ability to evade the human interferon response (9). By focusing on NDV, we can accurately depict the baseline network of transcription factor (TF) interactions that underlie a broad range of immune responses. Through comparative studies, this network will enable detailed analysis of other infections and greatly improve our understanding of the control mechanisms in antiviral immunity and the myriad ways through which pathogenic viruses subvert normal immune function.Systems biology methods combined with high-throughput experimental technologies are providing new insights into virus-host interactions (10, 11). Genome-wide transcriptional profiling has suggested that the DC antiviral response is characterized by temporal waves of gene activation, which may be controlled by different combinations of transcriptional regulators (1). Potential regulators can be implicated using direct approaches, such as differential expression of the TF mRNA (1) -regulatory motifs (12, 13). These methods typically provide a static view of the network. Other computational methods have been proposed to identify TFs driving time-dependent changes in expression, but these do not explicitly account for the regulation of the TF itself (14, 15). The most common approaches are based on the hypothesis that genes sharing a similar temporal profile are regulated by common TFs (16). In mammals, a variety of posttranscriptional ...

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“…Moreover, the mouse Cd36 gene is regulated in a tissue specific manner by PPARA in liver and by PPARG in adipose tissues [69]. Other TFBS sites predicted for the human CD36 5’ promoter region included RSRFC4, a myocyte enhancer factor 2A found in muscle-specific and ‘immediate early’ genes [70]; CART1, a paired-class homeodomain transcription factor [71]; FOXJ2, a fork head transcriptional activator which is active during early development [72]; XBP1, a transcription factor which is critical for cell fate determination in response to endoplasmic reticulum stress [73]; and CDC5, a transcription activator and cell cycle regulator [74]. Hepatic upregulation of CD36 transcription in human patients has been recently shown to be significantly associated with insulin resistance, hyperinsulinaemia and increased steatosis in non-alcoholic steatohepatitis and chronic hepatitis C [43].…”

Section: Resultsmentioning

confidence: 99%

“…Derived from the AceView website mature isoform variants are shown with capped 5’- and 3’- ends for the predicted mRNA sequences [62]; NM refers to the NCBI reference sequence; exons are in pink; the directions for transcription are shown as 5’ → 3’; sizes of mRNA sequences are shown in kilobases (kb); predicted transcription factor binding sites (TFBS) for human Cd36 are shown: CART1- a paired-class homeodomain transcription factor [71]; RSRFC4-myocyte enhancement factor 2A transcription factor [70]; XBP1-transcription factor [73]; FOXJ2-fork-head transcription factor [72]; CDC5-transcription activator and cell cycle regulator; [74]; PPARA-peroxisome proliferator-activated receptor alpha; and PPARG-peroxisome proliferator-activated receptor gamma [67,68]. …”

Section: Resultsmentioning

confidence: 99%

Comparative Studies of Vertebrate Platelet Glycoprotein 4 (CD36)

Holmes

2012

Biomolecules

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Platelet glycoprotein 4 (CD36) (or fatty acyl translocase [FAT], or scavenger receptor class B, member 3 [SCARB3]) is an essential cell surface and skeletal muscle outer mitochondrial membrane glycoprotein involved in multiple functions in the body. CD36 serves as a ligand receptor of thrombospondin, long chain fatty acids, oxidized low density lipoproteins (LDLs) and malaria-infected erythrocytes. CD36 also influences various diseases, including angiogenesis, thrombosis, atherosclerosis, malaria, diabetes, steatosis, dementia and obesity. Genetic deficiency of this protein results in significant changes in fatty acid and oxidized lipid uptake. Comparative CD36 amino acid sequences and structures and CD36 gene locations were examined using data from several vertebrate genome projects. Vertebrate CD36 sequences shared 53–100% identity as compared with 29–32% sequence identities with other CD36-like superfamily members, SCARB1 and SCARB2. At least eight vertebrate CD36 N-glycosylation sites were conserved which are required for membrane integration. Sequence alignments, key amino acid residues and predicted secondary structures were also studied. Three CD36 domains were identified including cytoplasmic, transmembrane and exoplasmic sequences. Conserved sequences included N- and C-terminal transmembrane glycines; and exoplasmic cysteine disulphide residues; TSP-1 and PE binding sites, Thr92 and His242, respectively; 17 conserved proline and 14 glycine residues, which may participate in forming CD36 ‘short loops’; and basic amino acid residues, and may contribute to fatty acid and thrombospondin binding. Vertebrate CD36 genes usually contained 12 coding exons. The human CD36 gene contained transcription factor binding sites (including PPARG and PPARA) contributing to a high gene expression level (6.6 times average). Phylogenetic analyses examined the relationships and potential evolutionary origins of the vertebrate CD36 gene with vertebrate SCARB1 and SCARB2 genes. These suggested that CD36 originated in an ancestral genome and was subsequently duplicated to form three vertebrate CD36 gene family members, SCARB1, SCARB2 and CD36.

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Human CART1, a Paired-Class Homeodomain Protein, Activates Transcription through Palindromic Binding Sites

Cited by 21 publications

References 15 publications

Meox Homeodomain Proteins Are Required forBapx1Expression in the Sclerotome and Activate Its Transcription by Direct Binding to Its Promoter

Meox Homeodomain Proteins Are Required forBapx1Expression in the Sclerotome and Activate Its Transcription by Direct Binding to Its Promoter

Antiviral Response Dictated by Choreographed Cascade of Transcription Factors

Comparative Studies of Vertebrate Platelet Glycoprotein 4 (CD36)

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