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Smooth Muscle Cell Genome Browser: Enabling the Identification of Novel Serum Response Factor Target Genes.

Lee MY, Park C, Berent RM, Park PJ, Fuchs R, Syn H, Chin A, Townsend J, Benson CC, Redelman D, Shen TW, Park JK, Miano JM, Sanders KM, Ro S - PLoS ONE (2015)

Bottom Line: The browser also serves as the first genome-wide map of SRF binding sites.The browser analysis revealed novel SMC-specific transcriptional variants and SRF target genes, which provided new and unique insights into the cellular and biological functions of the cells in gastrointestinal (GI) physiology.Our genome browser offers a new perspective into the alternative expression of genes in the context of SRF binding sites in SMCs and provides a valuable reference for future functional studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, United States of America; Department of Physiology, Wonkwang Digestive Disease Research Institute and Institute of Wonkwang Medical Science, School of Medicine, Wonkwang University, Iksan, Jeollabuk-do, Korea.

ABSTRACT
Genome-scale expression data on the absolute numbers of gene isoforms offers essential clues in cellular functions and biological processes. Smooth muscle cells (SMCs) perform a unique contractile function through expression of specific genes controlled by serum response factor (SRF), a transcription factor that binds to DNA sites known as the CArG boxes. To identify SRF-regulated genes specifically expressed in SMCs, we isolated SMC populations from mouse small intestine and colon, obtained their transcriptomes, and constructed an interactive SMC genome and CArGome browser. To our knowledge, this is the first online resource that provides a comprehensive library of all genetic transcripts expressed in primary SMCs. The browser also serves as the first genome-wide map of SRF binding sites. The browser analysis revealed novel SMC-specific transcriptional variants and SRF target genes, which provided new and unique insights into the cellular and biological functions of the cells in gastrointestinal (GI) physiology. The SRF target genes in SMCs, which were discovered in silico, were confirmed by proteomic analysis of SMC-specific Srf knockout mice. Our genome browser offers a new perspective into the alternative expression of genes in the context of SRF binding sites in SMCs and provides a valuable reference for future functional studies.

No MeSH data available.


Comparison of ion channel and transporter isoform genes expressed in SMCs.(A) Comparison of expression levels of ion channel isoforms in JSMCs and CSMCs. (B) Comparison of expression levels of ion transproter isoforms in JSMCs and CSMCs. (C) Calcium channel isoforms enriched in JSMCs and CSMCs. (D) SMC-specific calcium channel isoforms. Cell specificity was determined by comparative analysis of gene expression profiles among SMCs, ICC, and PDGFRα+ cells. (E) Voltage-dependent calcium channel isoforms (L-type, Cacna1c & d; T-type, Cacna1h & g; R-type, Cacna1e; P/Q-type, Cacna11) expressed in JSMCs. (F) Voltage-dedendent calcium channel isoforms in CSMCs.
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pone.0133751.g006: Comparison of ion channel and transporter isoform genes expressed in SMCs.(A) Comparison of expression levels of ion channel isoforms in JSMCs and CSMCs. (B) Comparison of expression levels of ion transproter isoforms in JSMCs and CSMCs. (C) Calcium channel isoforms enriched in JSMCs and CSMCs. (D) SMC-specific calcium channel isoforms. Cell specificity was determined by comparative analysis of gene expression profiles among SMCs, ICC, and PDGFRα+ cells. (E) Voltage-dependent calcium channel isoforms (L-type, Cacna1c & d; T-type, Cacna1h & g; R-type, Cacna1e; P/Q-type, Cacna11) expressed in JSMCs. (F) Voltage-dedendent calcium channel isoforms in CSMCs.

Mentions: Since contractile activity of SMCs is regulated by Ca2+ via ion channels and transporters [7,28], we used the transcriptome data to identify the ion channels and transporters that were differentially expressed in jejunal and colonic SMCs. In jejunal SMCs, a total of 442 ion channel and transporter isoforms (258 ion channels, 169 ion transporters, and 15 coupled ion channels and transporters) were expressed (S8 Table). Likewise in colonic SMCs, a total of 447 ion channel and transporter isoforms (263 ion channels, 168 ion transporters, and 16 coupled ion channels and transporters) were expressed (S9 Table). Not surprisingly, calcium channels were the most highly expressed type of ion channel in both JSMCs and CSMCs (Fig 6A). Furthermore, hydrogen transporters were the most dominantly expressed type of transporter in JSMCs and CSMCs (Fig 6B). To identify the most abundantly expressed ion channel and transporter classes in SMCs as well as SMC-specific isoforms, a more detailed analysis was performed.


Smooth Muscle Cell Genome Browser: Enabling the Identification of Novel Serum Response Factor Target Genes.

Lee MY, Park C, Berent RM, Park PJ, Fuchs R, Syn H, Chin A, Townsend J, Benson CC, Redelman D, Shen TW, Park JK, Miano JM, Sanders KM, Ro S - PLoS ONE (2015)

Comparison of ion channel and transporter isoform genes expressed in SMCs.(A) Comparison of expression levels of ion channel isoforms in JSMCs and CSMCs. (B) Comparison of expression levels of ion transproter isoforms in JSMCs and CSMCs. (C) Calcium channel isoforms enriched in JSMCs and CSMCs. (D) SMC-specific calcium channel isoforms. Cell specificity was determined by comparative analysis of gene expression profiles among SMCs, ICC, and PDGFRα+ cells. (E) Voltage-dependent calcium channel isoforms (L-type, Cacna1c & d; T-type, Cacna1h & g; R-type, Cacna1e; P/Q-type, Cacna11) expressed in JSMCs. (F) Voltage-dedendent calcium channel isoforms in CSMCs.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524680&req=5

pone.0133751.g006: Comparison of ion channel and transporter isoform genes expressed in SMCs.(A) Comparison of expression levels of ion channel isoforms in JSMCs and CSMCs. (B) Comparison of expression levels of ion transproter isoforms in JSMCs and CSMCs. (C) Calcium channel isoforms enriched in JSMCs and CSMCs. (D) SMC-specific calcium channel isoforms. Cell specificity was determined by comparative analysis of gene expression profiles among SMCs, ICC, and PDGFRα+ cells. (E) Voltage-dependent calcium channel isoforms (L-type, Cacna1c & d; T-type, Cacna1h & g; R-type, Cacna1e; P/Q-type, Cacna11) expressed in JSMCs. (F) Voltage-dedendent calcium channel isoforms in CSMCs.
Mentions: Since contractile activity of SMCs is regulated by Ca2+ via ion channels and transporters [7,28], we used the transcriptome data to identify the ion channels and transporters that were differentially expressed in jejunal and colonic SMCs. In jejunal SMCs, a total of 442 ion channel and transporter isoforms (258 ion channels, 169 ion transporters, and 15 coupled ion channels and transporters) were expressed (S8 Table). Likewise in colonic SMCs, a total of 447 ion channel and transporter isoforms (263 ion channels, 168 ion transporters, and 16 coupled ion channels and transporters) were expressed (S9 Table). Not surprisingly, calcium channels were the most highly expressed type of ion channel in both JSMCs and CSMCs (Fig 6A). Furthermore, hydrogen transporters were the most dominantly expressed type of transporter in JSMCs and CSMCs (Fig 6B). To identify the most abundantly expressed ion channel and transporter classes in SMCs as well as SMC-specific isoforms, a more detailed analysis was performed.

Bottom Line: The browser also serves as the first genome-wide map of SRF binding sites.The browser analysis revealed novel SMC-specific transcriptional variants and SRF target genes, which provided new and unique insights into the cellular and biological functions of the cells in gastrointestinal (GI) physiology.Our genome browser offers a new perspective into the alternative expression of genes in the context of SRF binding sites in SMCs and provides a valuable reference for future functional studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, United States of America; Department of Physiology, Wonkwang Digestive Disease Research Institute and Institute of Wonkwang Medical Science, School of Medicine, Wonkwang University, Iksan, Jeollabuk-do, Korea.

ABSTRACT
Genome-scale expression data on the absolute numbers of gene isoforms offers essential clues in cellular functions and biological processes. Smooth muscle cells (SMCs) perform a unique contractile function through expression of specific genes controlled by serum response factor (SRF), a transcription factor that binds to DNA sites known as the CArG boxes. To identify SRF-regulated genes specifically expressed in SMCs, we isolated SMC populations from mouse small intestine and colon, obtained their transcriptomes, and constructed an interactive SMC genome and CArGome browser. To our knowledge, this is the first online resource that provides a comprehensive library of all genetic transcripts expressed in primary SMCs. The browser also serves as the first genome-wide map of SRF binding sites. The browser analysis revealed novel SMC-specific transcriptional variants and SRF target genes, which provided new and unique insights into the cellular and biological functions of the cells in gastrointestinal (GI) physiology. The SRF target genes in SMCs, which were discovered in silico, were confirmed by proteomic analysis of SMC-specific Srf knockout mice. Our genome browser offers a new perspective into the alternative expression of genes in the context of SRF binding sites in SMCs and provides a valuable reference for future functional studies.

No MeSH data available.