Independent Repression of a GC-rich Housekeeping Gene by Sp1 and MAZ Involves the Same cis-Elements

Song, Jun; Ugai, Hideyo; Kanazawa, Ichiro; Sun, Kun; Yokoyama, Kazunari K.

doi:10.1074/jbc.m010658200

Cited by 62 publications

(57 citation statements)

References 53 publications

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“…The P-5 variant lies in the sequence GGGAGGG which has been shown to be a conserved DNA sequence motif in enhancer regions in a number of genes. 31,32 Strikingly, when we compared the human to mouse genomic sequence of the upstream region of GRK3, we found not only that this GGGAGGG element is not present in mouse, but also that the P-5 variant is located in a short DNA stretch which is unique to human sequence (see Figure 3). The P-6 variant is a single G deletion out of a run of 8 G's lying at the base of a potential hairpin structure formed by 12 G-C pairs.…”

Section: Discussionmentioning

confidence: 97%

Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder

et al. 2003

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In a genome-wide linkage survey, we have previously shown evidence suggesting that the chromosome 22q12 region contains a susceptibility locus for bipolar disorder (BPD). Two independent family sets yielded lod scores suggestive of linkage at markers in this region near the gene G protein receptor kinase 3 (GRK3). GRK3 is an excellent candidate risk gene for BPD since GRK3 is expressed widely in the brain, and since GRKs play key roles in the homologous desensitization of G protein-coupled receptor signaling. We have also previously shown GRK3 expression to be induced by amphetamine in an animal model of mania using microarraybased expression profiling. To identify possible functional mutations in GRK3, we sequenced the putative promoter region, all 21 exons, and intronic sequence flanking each exon, in 14-22 individuals with BPD. We found six sequence variants in the 5 0 -UTR/promoter region, but no coding or obvious splice variants. Transmission disequilibrium analyses of one set of 153 families indicated that two of the 5 0 -UTR/promoter variants are associated with BPD in families of northern European Caucasian ancestry. A supportive trend towards association to one of these two variants (P-5) was then subsequently obtained in an independent sample of 237 families. In the combined sample, the P-5 variant had an estimated allele frequency of 3% in bipolar subjects, and displayed a transmission to non-transmission ratio of 26 : 7.7 (v 2 ¼ 9.6, one-sided P value ¼ 0.0019). Altogether, these data support the hypothesis that a dysregulation in GRK3 expression alters signaling desensitization, and thereby predisposes to the development of BPD.

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Section: Discussionmentioning

confidence: 97%

Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder

et al. 2003

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“…Several other studies describe Sp1 as a negative regulator of transcription as well. For instance, disulfide bond A oxidoreductase-like protein (DsbA-L) in preadipocytes (49) and Myc-associated zinc finger protein (MAZ) expression in hepatocytes (50) have also been demonstrated to be negatively regulated by Sp1. Gene expression can also be repressed through recruitment of histone deacetylase or methyltransferase to Sp1 sites (51,52).…”

Section: Discussionmentioning

confidence: 99%

Spontaneous Glutamatergic Synaptic Activity Regulates Constitutive COX-2 Expression in Neurons OPPOSING ROLES FOR THE TRANSCRIPTION FACTORS CREB (cAMP RESPONSE ELEMENT BINDING) PROTEIN AND Sp1 (STIMULATORY PROTEIN-1)

Hewett

Shi

Gong

et al. 2016

Journal of Biological Chemistry

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Edited by Paul E. FraserBurgeoning evidence supports a role for cyclooxygenase metabolites in regulating membrane excitability in various forms of synaptic plasticity. Two cyclooxygenases, COX-1 and COX-2, catalyze the initial step in the metabolism of arachidonic acid to prostaglandins. COX-2 is generally considered inducible, but in glutamatergic neurons in some brain regions, including the cerebral cortex, it is constitutively expressed. However, the transcriptional mechanisms by which this occurs have not been elucidated. Here, we used quantitative PCR and also analyzed reporter gene expression in a mouse line carrying a construct consisting of a portion of the proximal promoter region of the mouse COX-2 gene upstream of luciferase cDNA to characterize COX-2 basal transcriptional regulation in cortical neurons. Extracts from the whole brain and from the cerebral cortex, hippocampus, and olfactory bulbs exhibited high luciferase activity. Moreover, constitutive COX-2 expression and luciferase activity were detected in cortical neurons, but not in cortical astrocytes, cultured from wild-type and transgenic mice, respectively. Constitutive COX-2 expression depended on spontaneous but not evoked excitatory synaptic activity and was shown to be N-methyl-D-aspartate receptor-dependent. Constitutive promoter activity was reduced in neurons transfected with a dominant-negative cAMP response element binding protein (CREB) and was eliminated by mutating the CRE-binding site on the COX-2 promoter. However, mutation of the stimulatory protein-1 (Sp1)-binding site resulted in an N-methyl-D-aspartate receptor-dependent enhancement of COX-2 promoter activity. Basal binding of the transcription factors CREB and Sp1 to the native neuronal COX-2 promoter was confirmed. In toto, our data suggest that spontaneous glutamatergic synaptic activity regulates constitutive neuronal COX-2 expression via Sp1 and CREB protein-dependent transcriptional mechanisms.The first committed reaction in the metabolism of arachidonic acid to prostaglandins and thromboxanes is catalyzed by two related heme-containing bis-oxygenases, cyclooxygenase (COX) 1 and 2. These enzymes share 90% similarity in amino acid sequence and exhibit nearly identical enzyme kinetics (1, 2). Both catalyze two separate reactions, the first metabolizing arachidonic acid to PGG 2 3 (cyclooxygenase reaction), an intermediate that is subsequently reduced in the second reaction to the product, PGH 2 (peroxidase reaction). PGH 2 is the substrate for various synthases that generate individual biologically active prostaglandins and thromboxanes, often in a cell typespecific manner (3). Although both metabolize arachidonic acid to PGH 2 , the transcriptional regulation of each isoform differs. The PTGS1 gene encoding COX-1 lacks a TATA box motif in its 5Ј promoter region and is generally constitutively active in cells (4, 5). In contrast, the promoter regulatory region of the PTGS2 gene encoding COX-2 is not typically active but can be strongly and rapidly induced under specific...

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“…16). As we found MAZ to be displaced from the GATA4 promoter after MYC expression in A549 cells, we predicted that the knockdown of MAZ in A549 cells could also lead to GATA4 upregulation.…”

Section: Protein Occupancy In the Gata4 Promoter Regionmentioning

confidence: 99%

MYC-Induced Epigenetic Activation of GATA4 in Lung Adenocarcinoma

Castro

Breiling

Luetkenhaus

et al. 2013

Molecular Cancer Research

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Human lung cancer is a disease with high incidence and accounts for most cancer-related deaths in both men and women. Metastasis is a common event in non-small cell lung carcinoma (NSCLC), diminishing the survival chance of the patients with this type of tumor. It has been shown that MYC is involved in the development of metastasis from NSCLC, but the mechanism underlying this switch remained to be identified. Here, we focus on GATA4 as a MYC target in the development of metastasis with origin in lung adenocarcinoma, the most common type of NSCLC. Epigenetic alterations at the GATA4 promoter level were observed after MYC expression in lung adenocarcinoma in vivo and in vitro. Such alterations include site-specific demethylation that accompanies the displacement of the MYC-associated zinc finger protein (MAZ) from the GATA4 promoter, which leads to GATA4 expression. Histone modification analysis of the GATA4 promoter revealed a switch from repressive histone marks to active histone marks after MYC binding, which corresponds to active GATA4 expression. Our results thus identify a novel epigenetic mechanism by which MYC activates GATA4 leading to metastasis in lung adenocarcinoma, suggesting novel potential targets for the development of antimetastatic therapy.

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Independent Repression of a GC-rich Housekeeping Gene by Sp1 and MAZ Involves the Same cis-Elements

Cited by 62 publications

References 53 publications

Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder

Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder

Spontaneous Glutamatergic Synaptic Activity Regulates Constitutive COX-2 Expression in Neurons OPPOSING ROLES FOR THE TRANSCRIPTION FACTORS CREB (cAMP RESPONSE ELEMENT BINDING) PROTEIN AND Sp1 (STIMULATORY PROTEIN-1)

MYC-Induced Epigenetic Activation of GATA4 in Lung Adenocarcinoma

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