A Palindromic Motif in the −2084 to −2078 Upstream Region is Essential for ABCA12 Promoter Function in Cultured Human Keratinocytes
ATP-binding cassette transporter family A member 12 (ABCA12) is a keratinocyte transmembrane lipid transporter that plays a critical role in preserving the skin permeability barrier. Biallelic loss of function of the ABCA12 gene is causative of some forms of recessive congenital ichthyosis, an intra...
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| Format: | Online |
| Language: | English |
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Nature Publishing Group
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206840/ |
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pubmed-4206840 |
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pubmed-42068402014-10-24 A Palindromic Motif in the −2084 to −2078 Upstream Region is Essential for ABCA12 Promoter Function in Cultured Human Keratinocytes Shimizu, Yoshitaka Ogawa, Yasushi Sugiura, Kazumitsu Takeda, Jun-ichi Sakai-Sawada, Kaori Yanagi, Teruki Kon, Atsushi Sawamura, Daisuke Shimizu, Hiroshi Akiyama, Masashi Article ATP-binding cassette transporter family A member 12 (ABCA12) is a keratinocyte transmembrane lipid transporter that plays a critical role in preserving the skin permeability barrier. Biallelic loss of function of the ABCA12 gene is causative of some forms of recessive congenital ichthyosis, an intractable disease marked by dry, thickened and scaly skin on the whole body. Genetic diagnosis is essential, although the results may occasionally be inconclusive, because some patients with low ABCA12 expression have one mutant allele and one apparently intact allele. Aside from aberrant splicing or deletion mutations, one possible explanation for such discrepancy is loss of promoter function. This study aims to elucidate the promoter region of ABCA12 and to locate the essential elements therein, thus providing the necessary information for genetic diagnostic screening of congenital ichthyosis. Close examination of the 2980-bp upstream regions of the ABCA12 gene revealed that a palindromic motif (tgagtca) at −2084 to −2078 is essential for the promoter function, and a short fragment of −2200/−1934 alone has potent promoter activity. Identification of the key promoter element of ABCA12 in this study may provide relevant information for genetic diagnosis of recessive congenital ichthyosis. Nature Publishing Group 2014-10-23 /pmc/articles/PMC4206840/ /pubmed/25338618 http://dx.doi.org/10.1038/srep06737 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Shimizu, Yoshitaka Ogawa, Yasushi Sugiura, Kazumitsu Takeda, Jun-ichi Sakai-Sawada, Kaori Yanagi, Teruki Kon, Atsushi Sawamura, Daisuke Shimizu, Hiroshi Akiyama, Masashi |
| spellingShingle |
Shimizu, Yoshitaka Ogawa, Yasushi Sugiura, Kazumitsu Takeda, Jun-ichi Sakai-Sawada, Kaori Yanagi, Teruki Kon, Atsushi Sawamura, Daisuke Shimizu, Hiroshi Akiyama, Masashi A Palindromic Motif in the −2084 to −2078 Upstream Region is Essential for ABCA12 Promoter Function in Cultured Human Keratinocytes |
| author_facet |
Shimizu, Yoshitaka Ogawa, Yasushi Sugiura, Kazumitsu Takeda, Jun-ichi Sakai-Sawada, Kaori Yanagi, Teruki Kon, Atsushi Sawamura, Daisuke Shimizu, Hiroshi Akiyama, Masashi |
| author_sort |
Shimizu, Yoshitaka |
| title |
A Palindromic Motif in the −2084 to −2078 Upstream Region is Essential for ABCA12 Promoter Function in Cultured Human Keratinocytes |
| title_short |
A Palindromic Motif in the −2084 to −2078 Upstream Region is Essential for ABCA12 Promoter Function in Cultured Human Keratinocytes |
| title_full |
A Palindromic Motif in the −2084 to −2078 Upstream Region is Essential for ABCA12 Promoter Function in Cultured Human Keratinocytes |
| title_fullStr |
A Palindromic Motif in the −2084 to −2078 Upstream Region is Essential for ABCA12 Promoter Function in Cultured Human Keratinocytes |
| title_full_unstemmed |
A Palindromic Motif in the −2084 to −2078 Upstream Region is Essential for ABCA12 Promoter Function in Cultured Human Keratinocytes |
| title_sort |
palindromic motif in the −2084 to −2078 upstream region is essential for abca12 promoter function in cultured human keratinocytes |
| description |
ATP-binding cassette transporter family A member 12 (ABCA12) is a keratinocyte transmembrane lipid transporter that plays a critical role in preserving the skin permeability barrier. Biallelic loss of function of the ABCA12 gene is causative of some forms of recessive congenital ichthyosis, an intractable disease marked by dry, thickened and scaly skin on the whole body. Genetic diagnosis is essential, although the results may occasionally be inconclusive, because some patients with low ABCA12 expression have one mutant allele and one apparently intact allele. Aside from aberrant splicing or deletion mutations, one possible explanation for such discrepancy is loss of promoter function. This study aims to elucidate the promoter region of ABCA12 and to locate the essential elements therein, thus providing the necessary information for genetic diagnostic screening of congenital ichthyosis. Close examination of the 2980-bp upstream regions of the ABCA12 gene revealed that a palindromic motif (tgagtca) at −2084 to −2078 is essential for the promoter function, and a short fragment of −2200/−1934 alone has potent promoter activity. Identification of the key promoter element of ABCA12 in this study may provide relevant information for genetic diagnosis of recessive congenital ichthyosis. |
| publisher |
Nature Publishing Group |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206840/ |
| _version_ |
1613147880429715456 |