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MAB21L4 regulates the TGF-β-induced expression of target genes in epidermal keratinocytes
Smad proteins transduce signals downstream of transforming growth factor-β (TGF-β) and are one of the factors that regulate the expression of genes related to diseases affecting the skin. In the present study, we identified MAB21L4, also known as male abnormal 21 like 4 or C2orf54, as the most up-re...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8969751/ https://www.ncbi.nlm.nih.gov/pubmed/34908107 http://dx.doi.org/10.1093/jb/mvab141 |
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author | Ogami, Tomohiro Tamura, Yusuke Toss, Kim Yuki, Keiko Morikawa, Masato Tsutsumi, Shuichi Aburatani, Hiroyuki Miyazawa, Keiji Miyazono, Kohei Koinuma, Daizo |
author_facet | Ogami, Tomohiro Tamura, Yusuke Toss, Kim Yuki, Keiko Morikawa, Masato Tsutsumi, Shuichi Aburatani, Hiroyuki Miyazawa, Keiji Miyazono, Kohei Koinuma, Daizo |
author_sort | Ogami, Tomohiro |
collection | PubMed |
description | Smad proteins transduce signals downstream of transforming growth factor-β (TGF-β) and are one of the factors that regulate the expression of genes related to diseases affecting the skin. In the present study, we identified MAB21L4, also known as male abnormal 21 like 4 or C2orf54, as the most up-regulated targets of TGF-β and Smad3 in differentiated human progenitor epidermal keratinocytes using chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq). We found that TGF-β induced expression of the barrier protein involucrin (encoded by the IVL gene). Transcriptional activity of the IVL promoter induced by TGF-β was inhibited by MAB21L4 siRNAs. Further analysis revealed that MAB21L4 siRNAs also down-regulated the expression of several target genes of TGF-β. MAB21L4 protein was located mainly in the cytosol, where it was physically bound to Smad3 and a transcriptional corepressor c-Ski. siRNAs for MAB21L4 did not inhibit the binding of Smad3 to their target genomic regions but down-regulated the acetylation of histone H3 lys 27 (H3K27ac), an active histone mark, near the Smad3 binding regions. These findings suggest that TGF-β-induced MAB21L4 up-regulates the gene expression induced by TGF-β, possibly through the inhibition of c-Ski via physical interaction in the cytosol. |
format | Online Article Text |
id | pubmed-8969751 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-89697512022-04-01 MAB21L4 regulates the TGF-β-induced expression of target genes in epidermal keratinocytes Ogami, Tomohiro Tamura, Yusuke Toss, Kim Yuki, Keiko Morikawa, Masato Tsutsumi, Shuichi Aburatani, Hiroyuki Miyazawa, Keiji Miyazono, Kohei Koinuma, Daizo J Biochem Regular Paper Smad proteins transduce signals downstream of transforming growth factor-β (TGF-β) and are one of the factors that regulate the expression of genes related to diseases affecting the skin. In the present study, we identified MAB21L4, also known as male abnormal 21 like 4 or C2orf54, as the most up-regulated targets of TGF-β and Smad3 in differentiated human progenitor epidermal keratinocytes using chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq). We found that TGF-β induced expression of the barrier protein involucrin (encoded by the IVL gene). Transcriptional activity of the IVL promoter induced by TGF-β was inhibited by MAB21L4 siRNAs. Further analysis revealed that MAB21L4 siRNAs also down-regulated the expression of several target genes of TGF-β. MAB21L4 protein was located mainly in the cytosol, where it was physically bound to Smad3 and a transcriptional corepressor c-Ski. siRNAs for MAB21L4 did not inhibit the binding of Smad3 to their target genomic regions but down-regulated the acetylation of histone H3 lys 27 (H3K27ac), an active histone mark, near the Smad3 binding regions. These findings suggest that TGF-β-induced MAB21L4 up-regulates the gene expression induced by TGF-β, possibly through the inhibition of c-Ski via physical interaction in the cytosol. Oxford University Press 2021-12-15 /pmc/articles/PMC8969751/ /pubmed/34908107 http://dx.doi.org/10.1093/jb/mvab141 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Japanese Biochemical Society. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Regular Paper Ogami, Tomohiro Tamura, Yusuke Toss, Kim Yuki, Keiko Morikawa, Masato Tsutsumi, Shuichi Aburatani, Hiroyuki Miyazawa, Keiji Miyazono, Kohei Koinuma, Daizo MAB21L4 regulates the TGF-β-induced expression of target genes in epidermal keratinocytes |
title | MAB21L4 regulates the TGF-β-induced expression of target genes in epidermal keratinocytes |
title_full | MAB21L4 regulates the TGF-β-induced expression of target genes in epidermal keratinocytes |
title_fullStr | MAB21L4 regulates the TGF-β-induced expression of target genes in epidermal keratinocytes |
title_full_unstemmed | MAB21L4 regulates the TGF-β-induced expression of target genes in epidermal keratinocytes |
title_short | MAB21L4 regulates the TGF-β-induced expression of target genes in epidermal keratinocytes |
title_sort | mab21l4 regulates the tgf-β-induced expression of target genes in epidermal keratinocytes |
topic | Regular Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8969751/ https://www.ncbi.nlm.nih.gov/pubmed/34908107 http://dx.doi.org/10.1093/jb/mvab141 |
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