Fine mapping genetic determinants of the highly variably expressed MHC gene ZFP57.
ZFP57 is an important transcriptional regulator involved in DNA methylation and genomic imprinting during development. Here we demonstrate that gene expression also occurs at a low level in adult peripheral blood cells and other tissues including the kidney and thymus, but is critically dependent on...
| Main Authors: | , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2014
|
| _version_ | 1797088291527327744 |
|---|---|
| author | Plant, K Fairfax, B Makino, S Vandiedonck, C Radhakrishnan, J Knight, J |
| author_facet | Plant, K Fairfax, B Makino, S Vandiedonck, C Radhakrishnan, J Knight, J |
| author_sort | Plant, K |
| collection | OXFORD |
| description | ZFP57 is an important transcriptional regulator involved in DNA methylation and genomic imprinting during development. Here we demonstrate that gene expression also occurs at a low level in adult peripheral blood cells and other tissues including the kidney and thymus, but is critically dependent on underlying local genetic variation within the MHC. We resolve a highly significant expression quantitative trait locus for ZFP57 involving single-nucleotide polymorphisms (SNPs) in the first intron of the gene co-localizing with a DNase I hypersensitive site and evidence of CTCF recruitment. These data identify ZFP57 as a candidate gene underlying reported MHC disease associations, notably for putative regulatory variants associated with cancer and HIV-1. The work highlights the role that ZFP57 may play in DNA methylation and epigenetic regulation beyond early development into adult life dependent on genetic background, with important potential implications for disease. |
| first_indexed | 2024-03-07T02:47:54Z |
| format | Journal article |
| id | oxford-uuid:aca5c2e2-cfbb-45e7-91bf-6e7c38bb12f2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:47:54Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:aca5c2e2-cfbb-45e7-91bf-6e7c38bb12f22022-03-27T03:30:24ZFine mapping genetic determinants of the highly variably expressed MHC gene ZFP57.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:aca5c2e2-cfbb-45e7-91bf-6e7c38bb12f2EnglishSymplectic Elements at Oxford2014Plant, KFairfax, BMakino, SVandiedonck, CRadhakrishnan, JKnight, JZFP57 is an important transcriptional regulator involved in DNA methylation and genomic imprinting during development. Here we demonstrate that gene expression also occurs at a low level in adult peripheral blood cells and other tissues including the kidney and thymus, but is critically dependent on underlying local genetic variation within the MHC. We resolve a highly significant expression quantitative trait locus for ZFP57 involving single-nucleotide polymorphisms (SNPs) in the first intron of the gene co-localizing with a DNase I hypersensitive site and evidence of CTCF recruitment. These data identify ZFP57 as a candidate gene underlying reported MHC disease associations, notably for putative regulatory variants associated with cancer and HIV-1. The work highlights the role that ZFP57 may play in DNA methylation and epigenetic regulation beyond early development into adult life dependent on genetic background, with important potential implications for disease. |
| spellingShingle | Plant, K Fairfax, B Makino, S Vandiedonck, C Radhakrishnan, J Knight, J Fine mapping genetic determinants of the highly variably expressed MHC gene ZFP57. |
| title | Fine mapping genetic determinants of the highly variably expressed MHC gene ZFP57. |
| title_full | Fine mapping genetic determinants of the highly variably expressed MHC gene ZFP57. |
| title_fullStr | Fine mapping genetic determinants of the highly variably expressed MHC gene ZFP57. |
| title_full_unstemmed | Fine mapping genetic determinants of the highly variably expressed MHC gene ZFP57. |
| title_short | Fine mapping genetic determinants of the highly variably expressed MHC gene ZFP57. |
| title_sort | fine mapping genetic determinants of the highly variably expressed mhc gene zfp57 |
| work_keys_str_mv | AT plantk finemappinggeneticdeterminantsofthehighlyvariablyexpressedmhcgenezfp57 AT fairfaxb finemappinggeneticdeterminantsofthehighlyvariablyexpressedmhcgenezfp57 AT makinos finemappinggeneticdeterminantsofthehighlyvariablyexpressedmhcgenezfp57 AT vandiedonckc finemappinggeneticdeterminantsofthehighlyvariablyexpressedmhcgenezfp57 AT radhakrishnanj finemappinggeneticdeterminantsofthehighlyvariablyexpressedmhcgenezfp57 AT knightj finemappinggeneticdeterminantsofthehighlyvariablyexpressedmhcgenezfp57 |