Transcriptional regulation of apolipoprotein A-IV by the transcription factor CREBH[S]
cAMP responsive element-binding protein H (CREBH) is an endoplasmic reticulum (ER) anchored transcription factor that is highly expressed in the liver and small intestine and implicated in nutrient metabolism and proinflammatory response. ApoA-IV is a glycoprotein secreted primarily by the intestine...
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| Format: | Article |
| Language: | English |
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Elsevier
2014-05-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520375040 |
| _version_ | 1818732509491363840 |
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| author | Xu Xu Jong-Gil Park Jae-Seon So Kyu Yeon Hur Ann-Hwee Lee |
| author_facet | Xu Xu Jong-Gil Park Jae-Seon So Kyu Yeon Hur Ann-Hwee Lee |
| author_sort | Xu Xu |
| collection | DOAJ |
| description | cAMP responsive element-binding protein H (CREBH) is an endoplasmic reticulum (ER) anchored transcription factor that is highly expressed in the liver and small intestine and implicated in nutrient metabolism and proinflammatory response. ApoA-IV is a glycoprotein secreted primarily by the intestine and to a lesser degree by the liver. ApoA-IV expression is suppressed in CREBH-deficient mice and strongly induced by enforced expression of the constitutively active form of CREBH, indicating that CREBH is the major transcription factor regulating Apoa4 gene expression. Here, we show that CREBH directly controls Apoa4 expression through two tandem CREBH binding sites (5′-CCACGTTG-3′) located on the promoter, which are conserved between human and mouse. Chromatin immunoprecipitation and electrophoretic mobility-shift assays demonstrated specific association of CREBH with the CREBH binding sites. We also demonstrated that a substantial amount of CREBH protein was basally processed to the active nuclear form in normal mouse liver, which was further increased in steatosis induced by high-fat diet or fasting, increasing apoA-IV expression. However, we failed to find significant activation of CREBH in response to ER stress, arguing against the critical role of CREBH in ER stress response. |
| first_indexed | 2024-12-17T23:34:42Z |
| format | Article |
| id | doaj.art-6139b05cd7de4a9b9dcec178dbfd6e9b |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T23:34:42Z |
| publishDate | 2014-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-6139b05cd7de4a9b9dcec178dbfd6e9b2022-12-21T21:28:35ZengElsevierJournal of Lipid Research0022-22752014-05-01555850859Transcriptional regulation of apolipoprotein A-IV by the transcription factor CREBH[S]Xu Xu0Jong-Gil Park1Jae-Seon So2Kyu Yeon Hur3Ann-Hwee Lee4Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NYDepartment of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NYDepartment of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NYDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaTo whom correspondence should be addressed; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NYcAMP responsive element-binding protein H (CREBH) is an endoplasmic reticulum (ER) anchored transcription factor that is highly expressed in the liver and small intestine and implicated in nutrient metabolism and proinflammatory response. ApoA-IV is a glycoprotein secreted primarily by the intestine and to a lesser degree by the liver. ApoA-IV expression is suppressed in CREBH-deficient mice and strongly induced by enforced expression of the constitutively active form of CREBH, indicating that CREBH is the major transcription factor regulating Apoa4 gene expression. Here, we show that CREBH directly controls Apoa4 expression through two tandem CREBH binding sites (5′-CCACGTTG-3′) located on the promoter, which are conserved between human and mouse. Chromatin immunoprecipitation and electrophoretic mobility-shift assays demonstrated specific association of CREBH with the CREBH binding sites. We also demonstrated that a substantial amount of CREBH protein was basally processed to the active nuclear form in normal mouse liver, which was further increased in steatosis induced by high-fat diet or fasting, increasing apoA-IV expression. However, we failed to find significant activation of CREBH in response to ER stress, arguing against the critical role of CREBH in ER stress response.http://www.sciencedirect.com/science/article/pii/S0022227520375040cAMP responsive element-binding protein HER stresshepatic steatosis |
| spellingShingle | Xu Xu Jong-Gil Park Jae-Seon So Kyu Yeon Hur Ann-Hwee Lee Transcriptional regulation of apolipoprotein A-IV by the transcription factor CREBH[S] Journal of Lipid Research cAMP responsive element-binding protein H ER stress hepatic steatosis |
| title | Transcriptional regulation of apolipoprotein A-IV by the transcription factor CREBH[S] |
| title_full | Transcriptional regulation of apolipoprotein A-IV by the transcription factor CREBH[S] |
| title_fullStr | Transcriptional regulation of apolipoprotein A-IV by the transcription factor CREBH[S] |
| title_full_unstemmed | Transcriptional regulation of apolipoprotein A-IV by the transcription factor CREBH[S] |
| title_short | Transcriptional regulation of apolipoprotein A-IV by the transcription factor CREBH[S] |
| title_sort | transcriptional regulation of apolipoprotein a iv by the transcription factor crebh s |
| topic | cAMP responsive element-binding protein H ER stress hepatic steatosis |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520375040 |
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