Biochemical characterization of the mammalian Cux2 protein

Gingras, Hélène; Cases, Olivier; Krasilnikova, Maria M.; Bérubé, Ginette; Nepveu, Alain

doi:10.1016/j.gene.2004.11.008

Cited by 40 publications

(52 citation statements)

References 29 publications

(59 reference statements)

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“…Both Cux1 and Cux2 are known to be expressed in postmitotic pyramidal neurons of upper cortical layers and in precursor cells of the proliferative ventricular and subventricular zones in the mouse cerebral cortex [18][19][20][21]. Cux2 particularly regulates the proliferation of intermediate neuronal precursors in the subventricular zone of the developing brain [22].…”

Section: Discussionmentioning

confidence: 99%

Possible association of CUX1 gene polymorphisms with antidepressant response in major depressive disorder

Sasayama

Hiraishi

Tatsumi³

et al. 2012

Pharmacogenomics J

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Association between response to antidepressant treatment and genetic polymorphisms was examined in two independent Japanese samples of patients with major depressive disorder (MDD). Genome-wide approach using the Illumina Human CNV370-quad Bead Chip was utilized in the analysis of the 92 MDD patients in the first sample.Eleven non-intergenic SNPs with uncorrected allelic P value < 0.0001 were selected for the subsequent association analyses in the second sample of 136 MDD patients.Difference in allele distribution between responders and nonresponders were found in the second stage sample for rs365836 and rs201522 of the CUX1 gene (P = 0.005 and 0.004, respectively). The allelic P values for rs365836 and rs201522 in both samples combined were 0.0000023 and 0.0000040, respectively. Our results provide the first evidence that polymorphisms of the CUX1 gene may be associated with response to antidepressant treatment in Japanese patients with MDD.

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Section: Discussionmentioning

confidence: 99%

Possible association of CUX1 gene polymorphisms with antidepressant response in major depressive disorder

Sasayama

Hiraishi

Tatsumi³

et al. 2012

Pharmacogenomics J

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“…The specificity of the Cux-2 antiserum has already been described (Gingras et al, 2005). In brief, Cux-2 protein is nuclear and is expressed only in neurons (Quaggin et al, 1996).…”

Section: Cux-1 and Cux-2 Protein Expressionmentioning

confidence: 98%

Expression of Cux‐1 and Cux‐2 in the developing somatosensory cortex of normal and barrel‐defective mice

et al. 2006

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Recently, two orthologues of the Drosophila homeobox Cut gene, Cux-1 and Cux-2, have been identified as restricted molecular markers of upper layer (II-IV) neurons in the murine cerebral cortex. We show that during early postnatal life, from P0 to P10, Cux-1 and Cux-2 mRNA are coexpressed in all primary sensory cortices. Antisera to Cux-1 and Cux-2 immunoreactivities preferentially label neurons in the barrel walls of the primary somatosensory cortex (S1). Subsequently, Cux-1 remains enriched in sensory cortices, whereas Cux-2 expression enlarges to comprise the frontal and insular areas. The laminar distribution of Cux-1 and Cux-2 differs: Cux-1 follows a layer IV to layer II decreasing gradient of expression, whereas Cux-2 expression is homogeneous across layers IV-II. No colocalization was found with GABA and birth dating experiments showed that Cux-1-positive neurons in layer IV are born during a restricted period, E13.5-E14.5, suggesting that Cux-1 is a useful molecular marker of the glutamatergic neurons of layer IV. We examined Cux-1 and Cux-2 in barrel-defective mouse strains, the VMAT2 KO, the MAOA KO, and the Adcyl 1 brl strain. A normal expression level of Cux-1 and Cux-2 was found in layer IV, despite the lack of segregation of the neurons as barrels. Conversely, in Reeler mice, Cux-1 and Cux-2 had a distinct laminar distribution: the Cux-1-positive neurons had an inverted deep localization, whereas the Cux-2-positive neurons were distributed throughout the cortical thickness, suggesting that Cux-2 expression is more widely expressed in the inverted cortex of reeler mutants. Our results indicate that Cux-1 is a useful marker of the layer IV neurons in S1, and that Cux-1 and Cux-2 are differently regulated in the upper layers of the cerebral cortex.

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“…ImageQuant software was used to quantify gel bands. The CUX EMSA probe is 5=-TCGAGACGATATCGATAAGCTTCTTTTC-3= (sense strand) (10). The antisense strand was end labeled with 32 P using T4 polynucleotide kinase, annealed to the sense strand, and purified on a BioSpin30 chromatography column (Bio-Rad Laboratories Inc., Hercules, CA).…”

Section: Animalsmentioning

confidence: 99%

“…CUX2 expression is ablated in adult female rat liver by hypophysectomy and can be induced in male liver to a normal female-like level by continuous GH infusion (23). CUX2 contains three Cut repeats and one homeodomain and displays a DNA binding specificity similar to that of the related protein CUX1 (15), but it exhibits more rapid DNA binding kinetics (10). Similar to CUX1, CUX2 can repress the p21 WAF1/CIP1/SDI1 promoter, but unlike CUX1, CUX2 does not activate the DNA polymerase ␣ promoter (10).…”

mentioning

confidence: 99%

“…CUX2 contains three Cut repeats and one homeodomain and displays a DNA binding specificity similar to that of the related protein CUX1 (15), but it exhibits more rapid DNA binding kinetics (10). Similar to CUX1, CUX2 can repress the p21 WAF1/CIP1/SDI1 promoter, but unlike CUX1, CUX2 does not activate the DNA polymerase ␣ promoter (10). Moreover, in neural tissue, CUX2 regulates dendritic branching and spine formation by directly repressing Xlr4b (7).…”

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confidence: 99%

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Impact of CUX2 on the Female Mouse Liver Transcriptome: Activation of Female-Biased Genes and Repression of Male-Biased Genes

Conforto

Zhang

Sherman

et al. 2012

Molecular and Cellular Biology

122

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The growth hormone-regulated transcription factors STAT5 and BCL6 coordinately regulate sex differences in mouse liver, primarily through effects in male liver, where male-biased genes are upregulated and many female-biased genes are actively repressed. Here we investigated whether CUX2, a highly female-specific liver transcription factor, contributes to an analogous regulatory network in female liver. Adenoviral overexpression of CUX2 in male liver induced 36% of female-biased genes and repressed 35% of male-biased genes. In female liver, CUX2 small interfering RNA (siRNA) preferentially induced genes repressed by adenovirus expressing CUX2 (adeno-CUX2) in male liver, and it preferentially repressed genes induced by adeno-CUX2 in male liver. CUX2 binding in female liver chromatin was enriched at sites of male-biased DNase hypersensitivity and at genomic regions showing male-enriched STAT5 binding. CUX2 binding was also enriched near genes repressed by adeno-CUX2 in male liver or induced by CUX2 siRNA in female liver but not at genes induced by adeno-CUX2, indicating that CUX2 binding is preferentially associated with gene repression. Nevertheless, direct CUX2 binding was seen at several highly female-specific genes that were positively regulated by CUX2, including A1bg, Cyp2b9, Cyp3a44, Tox, and Trim24. CUX2 expression and chromatin binding were high in immature male liver, where repression of adult male-biased genes and expression of adult femalebiased genes are common, suggesting that the downregulation of CUX2 in male liver at puberty contributes to the developmental changes establishing adult patterns of sex-specific gene expression. S ex differences in liver gene expression are widespread and affect a broad range of physiological processes, including steroid and drug metabolism, pheromone binding, and lipid metabolism. Hepatic sex-biased genes are regulated by growth hormone (GH) (35, 49), which is secreted by the pituitary gland in a sex-specific manner in rats, mice, and humans (16,28,44,53). Pituitary GH secretion is highly pulsatile in adult male rats and mice, where strong plasma peaks of GH are followed by periods when GH levels are below detection, whereas GH secretion is more frequent in females, resulting in a more continuous exposure to circulating GH. These sexually dimorphic plasma GH patterns stimulate sex differential patterns of tyrosine phosphorylation/activation and nuclear translocation of the transcription factors STAT5a and STAT5b (collectively, STAT5) (50). Thus, STAT5 activation is persistent in female liver but is intermittent in male liver, where it coincides with the onset of each plasma GH pulse (4, 43, 54). STAT5 positively regulates ϳ90% of male-biased genes and negatively regulates ϳ60% of female-biased genes in male mouse liver (5). STAT5 binding sites are found near 35 to 40% of sex-specific genes, suggesting they are directly regulated by STAT5 (54). However, a majority of sex-specific genes do not respond rapidly to GH-activated STAT5, suggesting indirect regulatory mechani...

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Biochemical characterization of the mammalian Cux2 protein

Cited by 40 publications

References 29 publications

Possible association of CUX1 gene polymorphisms with antidepressant response in major depressive disorder

Possible association of CUX1 gene polymorphisms with antidepressant response in major depressive disorder

Expression of Cux‐1 and Cux‐2 in the developing somatosensory cortex of normal and barrel‐defective mice

Impact of CUX2 on the Female Mouse Liver Transcriptome: Activation of Female-Biased Genes and Repression of Male-Biased Genes

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