Modulation of transcription factor binding and epigenetic regulation of the MLH1 CpG island and shore by polymorphism rs1800734 in colorectal cancer
The MLH1 promoter polymorphism rs1800734 is associated with MLH1 CpG island hypermethylation and expression loss in colorectal cancer (CRC). Conversely, variant rs1800734 is associated with MLH1 shore, but not island, hypomethylation in peripheral blood mononuclear cell DNA. To explore these distinc...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-06-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2017.1305527 |
| _version_ | 1797678949105401856 |
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| author | Andrea J. Savio Bharati Bapat |
| author_facet | Andrea J. Savio Bharati Bapat |
| author_sort | Andrea J. Savio |
| collection | DOAJ |
| description | The MLH1 promoter polymorphism rs1800734 is associated with MLH1 CpG island hypermethylation and expression loss in colorectal cancer (CRC). Conversely, variant rs1800734 is associated with MLH1 shore, but not island, hypomethylation in peripheral blood mononuclear cell DNA. To explore these distinct patterns, MLH1 CpG island and shore methylation was assessed in CRC cell lines stratified by rs1800734 genotype. Cell lines containing the variant A allele demonstrated MLH1 shore hypomethylation compared to wild type (GG). There was significant enrichment of transcription factor AP4 at the MLH1 promoter in GG and GA cell lines, but not the AA cell line, by chromatin immunoprecipitation studies. Preferential binding to the G allele was confirmed by sequencing in the GA cell line. The enhancer-associated histone modification H3K4me1 was enriched at the MLH1 shore; however, H3K27ac was not, indicating the shore is an inactive enhancer. These results demonstrate the role of variant rs1800734 in altering transcription factor binding as well as epigenetics at regions beyond the MLH1 CpG island in which it is located. |
| first_indexed | 2024-03-11T23:07:18Z |
| format | Article |
| id | doaj.art-41cc806c0dd24f2185d953ecf8c1bdf6 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:07:18Z |
| publishDate | 2017-06-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-41cc806c0dd24f2185d953ecf8c1bdf62023-09-21T12:43:12ZengTaylor & Francis GroupEpigenetics1559-22941559-23082017-06-0112644144810.1080/15592294.2017.13055271305527Modulation of transcription factor binding and epigenetic regulation of the MLH1 CpG island and shore by polymorphism rs1800734 in colorectal cancerAndrea J. Savio0Bharati Bapat1Lunenfeld-Tanenbaum Research Institute, Sinai Health SystemLunenfeld-Tanenbaum Research Institute, Sinai Health SystemThe MLH1 promoter polymorphism rs1800734 is associated with MLH1 CpG island hypermethylation and expression loss in colorectal cancer (CRC). Conversely, variant rs1800734 is associated with MLH1 shore, but not island, hypomethylation in peripheral blood mononuclear cell DNA. To explore these distinct patterns, MLH1 CpG island and shore methylation was assessed in CRC cell lines stratified by rs1800734 genotype. Cell lines containing the variant A allele demonstrated MLH1 shore hypomethylation compared to wild type (GG). There was significant enrichment of transcription factor AP4 at the MLH1 promoter in GG and GA cell lines, but not the AA cell line, by chromatin immunoprecipitation studies. Preferential binding to the G allele was confirmed by sequencing in the GA cell line. The enhancer-associated histone modification H3K4me1 was enriched at the MLH1 shore; however, H3K27ac was not, indicating the shore is an inactive enhancer. These results demonstrate the role of variant rs1800734 in altering transcription factor binding as well as epigenetics at regions beyond the MLH1 CpG island in which it is located.http://dx.doi.org/10.1080/15592294.2017.1305527chromatin immunoprecipitationcolorectal cancerdna methylationdna mismatch repairhistone modificationsmutl homolog 1single nucleotide polymorphisms |
| spellingShingle | Andrea J. Savio Bharati Bapat Modulation of transcription factor binding and epigenetic regulation of the MLH1 CpG island and shore by polymorphism rs1800734 in colorectal cancer Epigenetics chromatin immunoprecipitation colorectal cancer dna methylation dna mismatch repair histone modifications mutl homolog 1 single nucleotide polymorphisms |
| title | Modulation of transcription factor binding and epigenetic regulation of the MLH1 CpG island and shore by polymorphism rs1800734 in colorectal cancer |
| title_full | Modulation of transcription factor binding and epigenetic regulation of the MLH1 CpG island and shore by polymorphism rs1800734 in colorectal cancer |
| title_fullStr | Modulation of transcription factor binding and epigenetic regulation of the MLH1 CpG island and shore by polymorphism rs1800734 in colorectal cancer |
| title_full_unstemmed | Modulation of transcription factor binding and epigenetic regulation of the MLH1 CpG island and shore by polymorphism rs1800734 in colorectal cancer |
| title_short | Modulation of transcription factor binding and epigenetic regulation of the MLH1 CpG island and shore by polymorphism rs1800734 in colorectal cancer |
| title_sort | modulation of transcription factor binding and epigenetic regulation of the mlh1 cpg island and shore by polymorphism rs1800734 in colorectal cancer |
| topic | chromatin immunoprecipitation colorectal cancer dna methylation dna mismatch repair histone modifications mutl homolog 1 single nucleotide polymorphisms |
| url | http://dx.doi.org/10.1080/15592294.2017.1305527 |
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