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Erg is a crucial regulator of endocardial-mesenchymal transformation during cardiac valve morphogenesis.

Vijayaraj P, Le Bras A, Mitchell N, Kondo M, Juliao S, Wasserman M, Beeler D, Spokes K, Aird WC, Baldwin HS, Oettgen P - Development (2012)

Bottom Line: Four share a common translational start site encoded by exon 3 (Ex3) and are enriched in chondrocytes.The other three have a separate translational start site encoded by Ex4 and are enriched in endothelial cells.We show that Erg is required for the maintenance of the core EnMT regulatory factors that include Snail1 and Snail2 by binding to their promoter and intronic regions.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

ABSTRACT
During murine embryogenesis, the Ets factor Erg is highly expressed in endothelial cells of the developing vasculature and in articular chondrocytes of developing bone. We identified seven isoforms for the mouse Erg gene. Four share a common translational start site encoded by exon 3 (Ex3) and are enriched in chondrocytes. The other three have a separate translational start site encoded by Ex4 and are enriched in endothelial cells. Homozygous Erg(ΔEx3/ΔEx3) knockout mice are viable, fertile and do not display any overt phenotype. By contrast, homozygous Erg(ΔEx4/ΔEx4) knockout mice are embryonic lethal, which is associated with a marked reduction in endocardial-mesenchymal transformation (EnMT) during cardiac valve morphogenesis. We show that Erg is required for the maintenance of the core EnMT regulatory factors that include Snail1 and Snail2 by binding to their promoter and intronic regions.

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Genomic structure and expression of mouse Erg isoforms. (A) Genomic organization of Erg and representation of the different isoforms that result from the presence of two independent translation start sites within exons 3 and 4. The seven isoforms differ in the variable region and in the 5′ UTR. F1 and R1 denote forward and reverse qPCR primers used to identify Erg isoforms 1-4, whereas primers F2 and R2 were used to identify Erg isoforms 5-7. The pointed (PNT), variable and Ets domains are indicated. (B-E) Real-time PCR analysis of differential Erg isoform expression in various mouse cell lines. Isoforms 1-4 are predominantly expressed in non-endothelial cells (ECs) and in articular cartilage (B), whereas isoforms 5-7 are predominantly expressed in ECs (C). Similarly, adult organs enriched in blood vessels, such as heart and lung, predominantly express isoforms 5-7 (E), whereas organs such as the trachea with large amounts of chondrocytes express isoforms 1-4 (D). Error bars indicate s.d. of at least three independent qPCR reactions.
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Figure 1: Genomic structure and expression of mouse Erg isoforms. (A) Genomic organization of Erg and representation of the different isoforms that result from the presence of two independent translation start sites within exons 3 and 4. The seven isoforms differ in the variable region and in the 5′ UTR. F1 and R1 denote forward and reverse qPCR primers used to identify Erg isoforms 1-4, whereas primers F2 and R2 were used to identify Erg isoforms 5-7. The pointed (PNT), variable and Ets domains are indicated. (B-E) Real-time PCR analysis of differential Erg isoform expression in various mouse cell lines. Isoforms 1-4 are predominantly expressed in non-endothelial cells (ECs) and in articular cartilage (B), whereas isoforms 5-7 are predominantly expressed in ECs (C). Similarly, adult organs enriched in blood vessels, such as heart and lung, predominantly express isoforms 5-7 (E), whereas organs such as the trachea with large amounts of chondrocytes express isoforms 1-4 (D). Error bars indicate s.d. of at least three independent qPCR reactions.

Mentions: The mouse Erg gene contains 13 exons that span a region of ~225 kb on chromosome 16qC4 (Fig. 1A). By carefully analyzing the UCSC and Ensembl genome databases, we identified seven known transcript variants of mouse Erg. Isoforms 1-4 contain the same translational start site within exon 3. Isoforms 1 and 2 differ only in the 5′ UTR. By contrast, isoforms 3 and 4 have a truncated variable region, lacking either exon 9 or 10, respectively. Isoforms 5-7 have a separate translational start site within exon 4. Isoforms 5-7 differ by the presence or absence of exons 9 and 10 in the variable region. All isoforms contain the Ets DNA-binding domain and the pointed domain (PNT) known to be crucial for protein-protein interactions (Fig. 1A).


Erg is a crucial regulator of endocardial-mesenchymal transformation during cardiac valve morphogenesis.

Vijayaraj P, Le Bras A, Mitchell N, Kondo M, Juliao S, Wasserman M, Beeler D, Spokes K, Aird WC, Baldwin HS, Oettgen P - Development (2012)

Genomic structure and expression of mouse Erg isoforms. (A) Genomic organization of Erg and representation of the different isoforms that result from the presence of two independent translation start sites within exons 3 and 4. The seven isoforms differ in the variable region and in the 5′ UTR. F1 and R1 denote forward and reverse qPCR primers used to identify Erg isoforms 1-4, whereas primers F2 and R2 were used to identify Erg isoforms 5-7. The pointed (PNT), variable and Ets domains are indicated. (B-E) Real-time PCR analysis of differential Erg isoform expression in various mouse cell lines. Isoforms 1-4 are predominantly expressed in non-endothelial cells (ECs) and in articular cartilage (B), whereas isoforms 5-7 are predominantly expressed in ECs (C). Similarly, adult organs enriched in blood vessels, such as heart and lung, predominantly express isoforms 5-7 (E), whereas organs such as the trachea with large amounts of chondrocytes express isoforms 1-4 (D). Error bars indicate s.d. of at least three independent qPCR reactions.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472597&req=5

Figure 1: Genomic structure and expression of mouse Erg isoforms. (A) Genomic organization of Erg and representation of the different isoforms that result from the presence of two independent translation start sites within exons 3 and 4. The seven isoforms differ in the variable region and in the 5′ UTR. F1 and R1 denote forward and reverse qPCR primers used to identify Erg isoforms 1-4, whereas primers F2 and R2 were used to identify Erg isoforms 5-7. The pointed (PNT), variable and Ets domains are indicated. (B-E) Real-time PCR analysis of differential Erg isoform expression in various mouse cell lines. Isoforms 1-4 are predominantly expressed in non-endothelial cells (ECs) and in articular cartilage (B), whereas isoforms 5-7 are predominantly expressed in ECs (C). Similarly, adult organs enriched in blood vessels, such as heart and lung, predominantly express isoforms 5-7 (E), whereas organs such as the trachea with large amounts of chondrocytes express isoforms 1-4 (D). Error bars indicate s.d. of at least three independent qPCR reactions.
Mentions: The mouse Erg gene contains 13 exons that span a region of ~225 kb on chromosome 16qC4 (Fig. 1A). By carefully analyzing the UCSC and Ensembl genome databases, we identified seven known transcript variants of mouse Erg. Isoforms 1-4 contain the same translational start site within exon 3. Isoforms 1 and 2 differ only in the 5′ UTR. By contrast, isoforms 3 and 4 have a truncated variable region, lacking either exon 9 or 10, respectively. Isoforms 5-7 have a separate translational start site within exon 4. Isoforms 5-7 differ by the presence or absence of exons 9 and 10 in the variable region. All isoforms contain the Ets DNA-binding domain and the pointed domain (PNT) known to be crucial for protein-protein interactions (Fig. 1A).

Bottom Line: Four share a common translational start site encoded by exon 3 (Ex3) and are enriched in chondrocytes.The other three have a separate translational start site encoded by Ex4 and are enriched in endothelial cells.We show that Erg is required for the maintenance of the core EnMT regulatory factors that include Snail1 and Snail2 by binding to their promoter and intronic regions.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

ABSTRACT
During murine embryogenesis, the Ets factor Erg is highly expressed in endothelial cells of the developing vasculature and in articular chondrocytes of developing bone. We identified seven isoforms for the mouse Erg gene. Four share a common translational start site encoded by exon 3 (Ex3) and are enriched in chondrocytes. The other three have a separate translational start site encoded by Ex4 and are enriched in endothelial cells. Homozygous Erg(ΔEx3/ΔEx3) knockout mice are viable, fertile and do not display any overt phenotype. By contrast, homozygous Erg(ΔEx4/ΔEx4) knockout mice are embryonic lethal, which is associated with a marked reduction in endocardial-mesenchymal transformation (EnMT) during cardiac valve morphogenesis. We show that Erg is required for the maintenance of the core EnMT regulatory factors that include Snail1 and Snail2 by binding to their promoter and intronic regions.

Show MeSH
Related in: MedlinePlus