Gut microbiota-dependent adaptor molecule recruits DNA methyltransferase to the TLR4 gene in colonic epithelial cells to suppress inflammatory reactions Article Swipe
Hikari Narabayashi
,
Chiharu Koma
,
Kazuaki Nakata
,
Mion Ikegami
,
Yusuke Nakanishi
,
Jun Ogihara
,
Masato Tsuda
,
Akira Hosono
,
Shigemasa Hanazawa
,
Kyôko Takahashi
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fmolb.2022.1005136
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fmolb.2022.1005136
The intestine is inhabited by a large number of commensal bacteria that are immunologically non-self, potentially causing inflammation. However, in a healthy intestine, inflammation is strictly controlled at low levels to maintain homeostasis. We previously reported that the gut microbiota induce DNA methylation of the gene encoding Toll-like receptor (TLR) 4, a pattern recognition receptor that recognizes lipopolysaccharides of gram-negative bacteria, in colonic epithelial cells, suggesting its role in controlling intestinal inflammation. However, there remains a question of how gut microbiota cause methylation of only specific genes including TLR4, despite the fact that DNA methyltransferase (DNMT) is common to all genes targeted for methylation. Here, we identified RBM14 as an adaptor molecule that recruits DNMT to the TLR4 gene. RBM14 was shown to bind DNMT3 and be expressed at significantly higher levels in an intestinal epithelial cell (IEC) line with hypermethylated TLR4 gene than in an IEC line with hypomethylated TLR4 gene. In addition, RBM14 interacted with DNA regions of the TLR4 gene, and knockdown of RBM14 suppressed DNA methylation of the TLR4 gene in IECs. Furthermore, RBM14 expression was higher in colonic epithelial cells of conventional mice than in those of germ-free mice. Collectively, these results indicate that the gut microbiota induce methylation of the TLR4 gene in colonic epithelial cells by upregulating RBM14, which can recruit DNMT3 to the gene. The regulation of adaptor molecules such as RBM14, which bind to specific target genes and recruit DNMT, can explain, at least in part, how gut microbiota contribute to the maintenance of intestinal homeostasis through epigenetic control of specific gene expression in IECs.
Related Topics
Concepts
Biology
DNA methylation
TLR4
Methylation
Gene
Inflammation
DNA methyltransferase
Methyltransferase
Gene expression
Regulation of gene expression
Gene knockdown
Cell biology
Molecular biology
Immunology
Genetics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fmolb.2022.1005136
- https://www.frontiersin.org/articles/10.3389/fmolb.2022.1005136/pdf
- OA Status
- gold
- Cited By
- 13
- References
- 48
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4306969276
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4306969276Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fmolb.2022.1005136Digital Object Identifier
- Title
-
Gut microbiota-dependent adaptor molecule recruits DNA methyltransferase to the TLR4 gene in colonic epithelial cells to suppress inflammatory reactionsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-10-21Full publication date if available
- Authors
-
Hikari Narabayashi, Chiharu Koma, Kazuaki Nakata, Mion Ikegami, Yusuke Nakanishi, Jun Ogihara, Masato Tsuda, Akira Hosono, Shigemasa Hanazawa, Kyôko TakahashiList of authors in order
- Landing page
-
https://doi.org/10.3389/fmolb.2022.1005136Publisher landing page
- PDF URL
-
https://www.frontiersin.org/articles/10.3389/fmolb.2022.1005136/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.frontiersin.org/articles/10.3389/fmolb.2022.1005136/pdfDirect OA link when available
- Concepts
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Biology, DNA methylation, TLR4, Methylation, Gene, Inflammation, DNA methyltransferase, Methyltransferase, Gene expression, Regulation of gene expression, Gene knockdown, Cell biology, Molecular biology, Immunology, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
13Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 5, 2024: 2, 2023: 6Per-year citation counts (last 5 years)
- References (count)
-
48Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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