Expression of Id2 in the second heart field and cardiac defects in Id2 knock‐out mice

Jongbloed, Monique R.M.; Vicente‐Steijn, Rebecca; Douglas, Yvonne L.; Wisse, Lambertus J.; Mori, Kentaro; Yokota, Yoshifumi; Bartelings, Margot M.; Schalij, Martin J.; Mahtab, Edris A F; Poelmann, Robert E.; Groot, Adriana C. Gittenberger‐de

doi:10.1002/dvdy.22762

Cited by 27 publications

(18 citation statements)

References 174 publications

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“…It has been shown that Id2 is prominently expressed in the ventricular conduction system, including the atrioventricular bundle and the bundle branches, and is required for the development of the ventricular conduction system (Moskowitz et al, 2007). However, Id2 is largely absent in atrial myocardium (Jongbloed et al, 2011; Moskowitz et al, 2007). Our ChIP-seq and qRTPCR results suggest a direct repression role of COUP-TFII on the expression of Id2 (Figure 6F).…”

Section: Discussionmentioning

confidence: 99%

Atrial Identity Is Determined by a COUP-TFII Regulatory Network

et al. 2013

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SUMMARY Atria and ventricles exhibit distinct molecular profiles that produce structural and functional differences between the two cardiac compartments. However, factors that determine these differences remain largely undefined. Cardiomyocyte-specific COUP-TFII ablation produces ventricularized atria that exhibit ventricle-like action potentials, increased cardiomyocyte size, and development of extensive T-tubules. Changes in atrial characteristics are accompanied by alterations of 2584 genes, in which 81% of them were differentially expressed between atria and ventricles, suggesting that a major function of myocardial COUP-TFII is to determine the atrial identity. Chromatin immunoprecipitation assays using E13.5 atria identified classic atrial-ventricular identity genes Tbx5, Hey2, Irx4, MLC2v, MLC2a and MLC1a, among many other cardiac genes, as potential COUP-TFII direct targets. Collectively, our results reveal that COUP-TFII confers the atrial identity through direct binding and modulating expression of a broad spectrum of genes that have an impact on atrial development and function.

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Section: Discussionmentioning

confidence: 99%

Atrial Identity Is Determined by a COUP-TFII Regulatory Network

et al. 2013

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“…Knock out mouse models evaluating Id genes have demonstrated their essential role in development. Id2 null mice displays phenotypic abnormalities of retarded growth and neonatal morbidity due to a lactation defect [4], impaired chondrogenesis [5], B cell development [6] and severe cardiac defects [7]. Male Id2-/- mice also exhibit defects in spermatogenesis [8].…”

Section: Introductionmentioning

confidence: 99%

Id4 deficiency attenuates prostate development and promotes PIN-like lesions by regulating androgen receptor activity and expression of NKX3.1 and PTEN

et al. 2013

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BackgroundInhibitor of differentiation 4 (Id4), a member of the helix-loop-helix family of transcriptional regulators has emerged as a tumor suppressor in prostate cancer. Id4 is expressed in the normal prostate where its expression is also regulated by androgens. In this study we investigated the effect of loss of Id4 (Id4-/-) on adult prostate morphology.MethodsHistological analysis was performed on prostates from 6-8 weeks old Id4-/-, Id4+/- and Id4+/+ mice. Expression of Id1, Sox9, Myc, androgen receptor, Akt, p-Akt, Pten and Nkx3.1 was investigated by immunohistochemistry. Androgen receptor binding on NKX3.1 promoter was studied by chromatin immuno-precipitation. Id4 was either over-expressed or silenced in prostate cancer cell lines DU145 and LNCaP respectively followed by analysis of PTEN, NKX3.1 and Sox9 expression.ResultsId4-/- mice had smaller prostates with fewer tubules, smaller tubule diameters and subtle mPIN like lesions. Levels of androgen receptor were similar between wild type and Id4-/- prostate. Decreased NKX3.1 expression was in part due to decreased androgen receptor binding on NKX3.1 promoter in Id4-/- mice. The increase in the expression of Myc, Sox9, Id1, Ki67 and decrease in the expression of PTEN, Akt and phospho-AKT was associated with subtle mPIN like lesions in Id4-/- prostates. Finally, prostate cancer cell line models in which Id4 was either silenced or over-expressed confirmed that Id4 regulates NKX3.1, Sox9 and PTEN.ConclusionsOur results suggest that loss of Id4 attenuates normal prostate development and promotes hyperplasia/dysplasia with subtle mPIN like lesions characterized by gain of Myc and Id1 and loss of Nkx3.1 and Pten expression. One of the mechanisms by which Id4 may regulate normal prostate development is through regulating androgen receptor binding to respective response elements such as those on NKX3.1 promoter. In spite of these complex alterations, large neoplastic lesions in Id4-/- prostates were not observed suggesting the possibility of mechanisms/pathways such as loss of Akt that could restrain the formation of significant pre-cancerous lesions.

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“…Id2 participates in various processes during the heart development, including myogenesis, neurogenesis, cell growth and cell differentiation [13][14][15]. Removal of Id2 from the cardiac neural crest results in structural defects in the outflow tract (such as the common arterial trunk), and a significant loss would be observed in the Id2 expression in the outflow tract.…”

Section: Correlation Analysis Between Id2 Gene Methylation Level and mentioning

confidence: 99%

No association between Id2 gene methylation and tetralogy of Fallot: a case-control study in China children

Yan

Zhang

Guo

et al. 2018

Biotechnology & Biotechnological Equipment

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The aim of this case-control study was to investigate the correlation between the methylation levels of inhibitor of DNA binding 2 (Id2) gene and the incidence of tetralogy of Fallot (TOF) in children. The study included 31 TOF and 32 healthy control children. The methylation status of the Id2 gene was determined with time-of-flight mass spectrometry. Peripheral blood indices were detected, and their correlations with Id2 gene methylation were analyzed. Methylation analysis showed that there was no significant difference in the Id2 gene methylation level between the control and TOF groups (P > 0.05). After controlling the factors of gender, age, height and body weight, the analysis showed that there was no correlation between the methylation levels at each Id2 site and the red blood cells (RBC), hemoglobin (HGB) or hematocrit (HCT) (P > 0.05). However, the methylation levels at the CpG-16 and CpG-18.19 sites of the Id2 gene were negatively correlated with the mean corpuscular hemoglobin (MCH) (r = ¡0.337, P = 0.009; r = ¡0.392, P = 0.002) and mean corpuscular hemoglobin concentration (MCHC) (r = ¡0.363, P = 0.005; r = ¡0.286, P = 0.028), respectively. Our results suggest that the Id2 methylation might not be associated with the incidence of TOF. These results might contribute to the understanding of the etiology and mechanism of TOF in clinic.

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Expression of Id2 in the second heart field and cardiac defects in Id2 knock‐out mice

Cited by 27 publications

References 174 publications

Atrial Identity Is Determined by a COUP-TFII Regulatory Network

Atrial Identity Is Determined by a COUP-TFII Regulatory Network

Id4 deficiency attenuates prostate development and promotes PIN-like lesions by regulating androgen receptor activity and expression of NKX3.1 and PTEN

No association between Id2 gene methylation and tetralogy of Fallot: a case-control study in China children

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