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CAGE-defined promoter regions of the genes implicated in Rett Syndrome.

Vitezic M, Bertin N, Andersson R, Lipovich L, Kawaji H, Lassmann T, Sandelin A, Heutink P, Goldowitz D, Ha T, Zhang P, Patrizi A, Fagiolini M, Forrest AR, Carninci P, Saxena A, FANTOM Consorti - BMC Genomics (2014)

Bottom Line: We show that FOXG1 expression is poorly correlated with the expression of MECP2 and CDKL5.We identify promoter shapes for each TSS, the predicted location of enhancers for each gene and the common transcription factors likely to regulate the three genes.Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum.

View Article: PubMed Central - PubMed

Affiliation: Omics Science Center, RIKEN Yokohama Institute, Omics Science Center (OSC), 1-17-22 Suehiro cho, Tsurumi ku, Yokohama, Japan. mvitezic@gmail.com.

ABSTRACT

Background: Mutations in three functionally diverse genes cause Rett Syndrome. Although the functions of Forkhead box G1 (FOXG1), Methyl CpG binding protein 2 (MECP2) and Cyclin-dependent kinase-like 5 (CDKL5) have been studied individually, not much is known about their relation to each other with respect to expression levels and regulatory regions. Here we analyzed data from hundreds of mouse and human samples included in the FANTOM5 project, to identify transcript initiation sites, expression levels, expression correlations and regulatory regions of the three genes.

Results: Our investigations reveal the predominantly used transcription start sites (TSSs) for each gene including novel transcription start sites for FOXG1. We show that FOXG1 expression is poorly correlated with the expression of MECP2 and CDKL5. We identify promoter shapes for each TSS, the predicted location of enhancers for each gene and the common transcription factors likely to regulate the three genes. Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum.

Conclusions: Our analyses provide a comprehensive picture of the regulatory regions of the three genes involved in Rett Syndrome.

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Related in: MedlinePlus

Mouse gene models derived from FANTOM5 TSS and ENCODE ChIP data. Gene models for Foxg1(panel a), Mecp2(panel b) and Cdkl5(panel c) were drawn for the main TSS for each gene and the ENCODE histone ChIP marks for 8 week mouse cortex. For Foxg1, the enhancer mark was 1 kb upstream and the promoter mark was 1.1 kb downstream of the TSS. For Mecp2, the TSS was upstream of the overlapping promoter and enhancer mark. For Cdkl5, the TSS was within the promoter and the enhancer was upstream of the TSS.
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Fig4: Mouse gene models derived from FANTOM5 TSS and ENCODE ChIP data. Gene models for Foxg1(panel a), Mecp2(panel b) and Cdkl5(panel c) were drawn for the main TSS for each gene and the ENCODE histone ChIP marks for 8 week mouse cortex. For Foxg1, the enhancer mark was 1 kb upstream and the promoter mark was 1.1 kb downstream of the TSS. For Mecp2, the TSS was upstream of the overlapping promoter and enhancer mark. For Cdkl5, the TSS was within the promoter and the enhancer was upstream of the TSS.

Mentions: Since all three genes were found highly expressed in the cortex, we used ENCODE ChIP tracks for 8 week old cortex for this analysis. Based on our results we derived gene models for the three genes in mouse cortex (Figure 4). Our data revealed that the investigated regulatory marks for mouse Foxg1, were distinct and non-overlapping (Additional file 12: Table S5). We found that the main TSSs pA@Foxg1 and pB@Foxg1 were located between an enhancer specific histone mark upstream and a promoter specific histone mark downstream (Figure 4a and Additional file 12: Table S5). In contrast, for Mecp2, we found the enhancer and promoter specific histone marks to coincide in this tissue (Figure 4b, Additional file 12: Table S5). The Mecp2 TSSs p1@Mecp2 and p2@Mecp2 were upstream but within 500 bp of the histone specific marks for enhancer and promoter. For Cdkl5, we found a partial overlap between enhancer and promoter specific histone marks. The p1@Cdkl5 was located within the promoter specific histone mark while the enhancer specific histone mark was found upstream (Figure 4c, Additional file 12: Table S5). The TSS p2@Cdkl5 was also located within 500 bp of these marks.Figure 4


CAGE-defined promoter regions of the genes implicated in Rett Syndrome.

Vitezic M, Bertin N, Andersson R, Lipovich L, Kawaji H, Lassmann T, Sandelin A, Heutink P, Goldowitz D, Ha T, Zhang P, Patrizi A, Fagiolini M, Forrest AR, Carninci P, Saxena A, FANTOM Consorti - BMC Genomics (2014)

Mouse gene models derived from FANTOM5 TSS and ENCODE ChIP data. Gene models for Foxg1(panel a), Mecp2(panel b) and Cdkl5(panel c) were drawn for the main TSS for each gene and the ENCODE histone ChIP marks for 8 week mouse cortex. For Foxg1, the enhancer mark was 1 kb upstream and the promoter mark was 1.1 kb downstream of the TSS. For Mecp2, the TSS was upstream of the overlapping promoter and enhancer mark. For Cdkl5, the TSS was within the promoter and the enhancer was upstream of the TSS.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4522966&req=5

Fig4: Mouse gene models derived from FANTOM5 TSS and ENCODE ChIP data. Gene models for Foxg1(panel a), Mecp2(panel b) and Cdkl5(panel c) were drawn for the main TSS for each gene and the ENCODE histone ChIP marks for 8 week mouse cortex. For Foxg1, the enhancer mark was 1 kb upstream and the promoter mark was 1.1 kb downstream of the TSS. For Mecp2, the TSS was upstream of the overlapping promoter and enhancer mark. For Cdkl5, the TSS was within the promoter and the enhancer was upstream of the TSS.
Mentions: Since all three genes were found highly expressed in the cortex, we used ENCODE ChIP tracks for 8 week old cortex for this analysis. Based on our results we derived gene models for the three genes in mouse cortex (Figure 4). Our data revealed that the investigated regulatory marks for mouse Foxg1, were distinct and non-overlapping (Additional file 12: Table S5). We found that the main TSSs pA@Foxg1 and pB@Foxg1 were located between an enhancer specific histone mark upstream and a promoter specific histone mark downstream (Figure 4a and Additional file 12: Table S5). In contrast, for Mecp2, we found the enhancer and promoter specific histone marks to coincide in this tissue (Figure 4b, Additional file 12: Table S5). The Mecp2 TSSs p1@Mecp2 and p2@Mecp2 were upstream but within 500 bp of the histone specific marks for enhancer and promoter. For Cdkl5, we found a partial overlap between enhancer and promoter specific histone marks. The p1@Cdkl5 was located within the promoter specific histone mark while the enhancer specific histone mark was found upstream (Figure 4c, Additional file 12: Table S5). The TSS p2@Cdkl5 was also located within 500 bp of these marks.Figure 4

Bottom Line: We show that FOXG1 expression is poorly correlated with the expression of MECP2 and CDKL5.We identify promoter shapes for each TSS, the predicted location of enhancers for each gene and the common transcription factors likely to regulate the three genes.Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum.

View Article: PubMed Central - PubMed

Affiliation: Omics Science Center, RIKEN Yokohama Institute, Omics Science Center (OSC), 1-17-22 Suehiro cho, Tsurumi ku, Yokohama, Japan. mvitezic@gmail.com.

ABSTRACT

Background: Mutations in three functionally diverse genes cause Rett Syndrome. Although the functions of Forkhead box G1 (FOXG1), Methyl CpG binding protein 2 (MECP2) and Cyclin-dependent kinase-like 5 (CDKL5) have been studied individually, not much is known about their relation to each other with respect to expression levels and regulatory regions. Here we analyzed data from hundreds of mouse and human samples included in the FANTOM5 project, to identify transcript initiation sites, expression levels, expression correlations and regulatory regions of the three genes.

Results: Our investigations reveal the predominantly used transcription start sites (TSSs) for each gene including novel transcription start sites for FOXG1. We show that FOXG1 expression is poorly correlated with the expression of MECP2 and CDKL5. We identify promoter shapes for each TSS, the predicted location of enhancers for each gene and the common transcription factors likely to regulate the three genes. Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum.

Conclusions: Our analyses provide a comprehensive picture of the regulatory regions of the three genes involved in Rett Syndrome.

Show MeSH
Related in: MedlinePlus