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Genes associated with the cis-regulatory functions of intragenic LINE-1 elements.

Wanichnopparat W, Suwanwongse K, Pin-On P, Aporntewan C, Mutirangura A - BMC Genomics (2013)

Bottom Line: After a permutation based statistical analysis and a multiple hypothesis testing, 73 genes were found to induce significant regulatory changes (upregulation and/or downregulation) in genes with L1s.In detail, 5 genes were found to induce both the upregulation and downregulation of genes with L1s, whereas 27 and 37 genes induced the downregulation and upregulation, respectively, of genes with L1s.Moreover, the siRNA-regulating genes containing L1s possess a variety of molecular functions, are responsible for many cellular phenotypes and are associated with a number of diseases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

ABSTRACT

Background: Thousands of intragenic long interspersed element 1 sequences (LINE-1 elements or L1s) reside within genes. These intragenic L1 sequences are conserved and regulate the expression of their host genes. When L1 methylation is decreased, either through chemical induction or in cancer, the intragenic L1 transcription is increased. The resulting L1 mRNAs form RISC complexes with pre-mRNA to degrade the complementary mRNA. In this study, we screened for genes that are involved in intragenic L1 regulation networks.

Results: Genes containing L1s were obtained from L1Base (http://l1base.molgen.mpg.de). The expression profiles of 205 genes in 516 gene knockdown experiments were obtained from the Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo). The expression levels of the genes with and without L1s were compared using Pearson's chi-squared test. After a permutation based statistical analysis and a multiple hypothesis testing, 73 genes were found to induce significant regulatory changes (upregulation and/or downregulation) in genes with L1s. In detail, 5 genes were found to induce both the upregulation and downregulation of genes with L1s, whereas 27 and 37 genes induced the downregulation and upregulation, respectively, of genes with L1s. These regulations sometimes differed depending on the cell type and the orientation of the intragenic L1s. Moreover, the siRNA-regulating genes containing L1s possess a variety of molecular functions, are responsible for many cellular phenotypes and are associated with a number of diseases.

Conclusions: Cells use intragenic L1s as cis-regulatory elements within gene bodies to modulate gene expression. There may be several mechanisms by which L1s mediate gene expression. Intragenic L1s may be involved in the regulation of several biological processes, including DNA damage and repair, inflammation, immune function, embryogenesis, cell differentiation, cellular response to external stimuli and hormonal responses. Furthermore, in addition to cancer, intragenic L1s may alter gene expression in a variety of diseases and abnormalities.

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The figure shows the molecular functions, the molecular and cellular phenotypes and the associated diseases and abnormalities of significant siRNA genes.
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Figure 4: The figure shows the molecular functions, the molecular and cellular phenotypes and the associated diseases and abnormalities of significant siRNA genes.

Mentions: We reviewed the genes that regulate genes with L1s, their molecular functions, and their association with cellular phenotypes. These genes produce several types of proteins, such as transcriptional factors, topoisomerase, histone modification, RNA elongation, signal transduction, membrane receptors and extracellular growth factors (Figure 4 and Additional file 2: Table S2). The genes regulating genes with L1s play a role in a number of cellular phenotypes, such as cell differentiation, cell proliferation, hormonal response, cell homeostasis, stem cell and viral infection, and have been reported to be associated with a number of diseases, such as cancer, hormone-related diseases, neurodegenerative diseases, schizophrenia, diabetes, and autoimmune and inflammation-related diseases (Figure 4 and Additional file 2: Table S2).


Genes associated with the cis-regulatory functions of intragenic LINE-1 elements.

Wanichnopparat W, Suwanwongse K, Pin-On P, Aporntewan C, Mutirangura A - BMC Genomics (2013)

The figure shows the molecular functions, the molecular and cellular phenotypes and the associated diseases and abnormalities of significant siRNA genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643820&req=5

Figure 4: The figure shows the molecular functions, the molecular and cellular phenotypes and the associated diseases and abnormalities of significant siRNA genes.
Mentions: We reviewed the genes that regulate genes with L1s, their molecular functions, and their association with cellular phenotypes. These genes produce several types of proteins, such as transcriptional factors, topoisomerase, histone modification, RNA elongation, signal transduction, membrane receptors and extracellular growth factors (Figure 4 and Additional file 2: Table S2). The genes regulating genes with L1s play a role in a number of cellular phenotypes, such as cell differentiation, cell proliferation, hormonal response, cell homeostasis, stem cell and viral infection, and have been reported to be associated with a number of diseases, such as cancer, hormone-related diseases, neurodegenerative diseases, schizophrenia, diabetes, and autoimmune and inflammation-related diseases (Figure 4 and Additional file 2: Table S2).

Bottom Line: After a permutation based statistical analysis and a multiple hypothesis testing, 73 genes were found to induce significant regulatory changes (upregulation and/or downregulation) in genes with L1s.In detail, 5 genes were found to induce both the upregulation and downregulation of genes with L1s, whereas 27 and 37 genes induced the downregulation and upregulation, respectively, of genes with L1s.Moreover, the siRNA-regulating genes containing L1s possess a variety of molecular functions, are responsible for many cellular phenotypes and are associated with a number of diseases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

ABSTRACT

Background: Thousands of intragenic long interspersed element 1 sequences (LINE-1 elements or L1s) reside within genes. These intragenic L1 sequences are conserved and regulate the expression of their host genes. When L1 methylation is decreased, either through chemical induction or in cancer, the intragenic L1 transcription is increased. The resulting L1 mRNAs form RISC complexes with pre-mRNA to degrade the complementary mRNA. In this study, we screened for genes that are involved in intragenic L1 regulation networks.

Results: Genes containing L1s were obtained from L1Base (http://l1base.molgen.mpg.de). The expression profiles of 205 genes in 516 gene knockdown experiments were obtained from the Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo). The expression levels of the genes with and without L1s were compared using Pearson's chi-squared test. After a permutation based statistical analysis and a multiple hypothesis testing, 73 genes were found to induce significant regulatory changes (upregulation and/or downregulation) in genes with L1s. In detail, 5 genes were found to induce both the upregulation and downregulation of genes with L1s, whereas 27 and 37 genes induced the downregulation and upregulation, respectively, of genes with L1s. These regulations sometimes differed depending on the cell type and the orientation of the intragenic L1s. Moreover, the siRNA-regulating genes containing L1s possess a variety of molecular functions, are responsible for many cellular phenotypes and are associated with a number of diseases.

Conclusions: Cells use intragenic L1s as cis-regulatory elements within gene bodies to modulate gene expression. There may be several mechanisms by which L1s mediate gene expression. Intragenic L1s may be involved in the regulation of several biological processes, including DNA damage and repair, inflammation, immune function, embryogenesis, cell differentiation, cellular response to external stimuli and hormonal responses. Furthermore, in addition to cancer, intragenic L1s may alter gene expression in a variety of diseases and abnormalities.

Show MeSH
Related in: MedlinePlus