Methylation of an intragenic alternative promoter regulates transcription of GARP

Haupt, Sonja; Söntgerath, V.; Leipe, Jan; Schulze‐Koops, Hendrik; Skapenko, Alla

doi:10.1016/j.bbagrm.2015.11.003

Cited by 17 publications

(17 citation statements)

References 33 publications

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“…It is well established that in addition to chromatin accessibility, the presence of active histone marks, especially histone H3K4me1 and H3K27ac, is necessary for transcription factor binding and is correlated with the transcription factor binding sites . For example, a simultaneous increase in the levels of promoter histone H3K4 methylation, histone H3 acetylation, and NFAT transcription factor binding has been associated with the active gene transcription . Therefore, the status of these histone modifications was investigated in chromatin‐accessible regions of the eight most over‐expressed genes that were associated with the open chromatin regions in NASH‐derived HCC.…”

Section: Resultsmentioning

confidence: 99%

“…23,[29][30][31][32] For example, a simultaneous increase in the levels of promoter histone H3K4 methylation, histone H3 acetylation, and NFAT transcription factor binding has been associated with the active gene transcription. 33 Therefore, the status of these histone modifications was investigated in chromatin-accessible regions of the eight most over-expressed genes that were associated with the open chromatin regions in NASH-derived HCC. Figure 4 shows that seven of the eight most up-regulated genes exhibited a greater level for one or both of these active histone marks in gene chromatin-accessible regions in NASH-derived HCC as compared to that in the livers of control mice.…”

Section: Histone H3k4me1 and H3k27ac Marks Are Enriched At Chromatimentioning

confidence: 99%

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Identification of chromatin‐accessible domains in non‐alcoholic steatohepatitis‐derived hepatocellular carcinoma

Dechassa

Tryndyak

Conti

et al. 2018

Molecular Carcinogenesis

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Non-alcoholic steatohepatitis (NASH) is becoming one of the major causes of hepatocellular carcinoma (HCC) in the United States and Western countries; however, the molecular mechanisms associated with NASH-related liver carcinogenesis are not well understood. In the present study, we investigated cancer-associated chromatin alterations using a model that resembles the development of NASH-related HCC in humans. An assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) identified 1677 tumor-specific chromatin-accessible regions in NASH-derived HCC tissue samples. Using a combined analysis of ATAC-seq and global gene expression data, we identified 199 differentially expressed genes, 139 up-regulated and 60 down-regulated. Interestingly, 15 of the 139 up-regulated genes had accessible chromatin sites within 5 Kb of the transcription start site (TSS), including Apoa4, Anxa2, Serpine1, Igfbp1, and Tubb2a, genes critically involved in the development of NASH and HCC. We demonstrate that the mechanism for the up-regulation of these genes is associated with the enrichment of chromatin-accessible regions by transcription factors, especially NFATC2, and histone H3K4me1 and H3K27ac gene transcription-activating marks. These data underline the important role of chromatin accessibility perturbations in reshaping of the chromatin landscape in NASH-related HCC.

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Section: Resultsmentioning

confidence: 99%

Section: Histone H3k4me1 and H3k27ac Marks Are Enriched At Chromatimentioning

confidence: 99%

Identification of chromatin‐accessible domains in non‐alcoholic steatohepatitis‐derived hepatocellular carcinoma

Dechassa

Tryndyak

Conti

et al. 2018

Molecular Carcinogenesis

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“…NF-κB is the common downstream molecule of multiple MyD88-dependent TLR signaling cascades (70). It is possible that TLR signaling induces GARP expression via NF-κB, as suggested by the presence of a putative NF-κB-binding site in the promoter region of Lrrc32 (82). However, further study is necessary to clarify how GARP is regulated by TLR pathways.…”

Section: Discussionmentioning

confidence: 99%

B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex

Wallace¹,

Wu²,

Salem³

et al. 2018

JCI Insight

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“…In contrast, the less pronounced methylation status of P1 in Tregs allowed the binding of its nuclear master transcription factor forkhead box P3 (FoxP3) that remodels the promoter region toward an open configuration status. This allows the subsequent binding of nuclear factor of activated T cells (NFAT) and nuclear factor-κB (NF-κB) to drive the transcription of the GARP gene [ 32 ]. A clear example of this FoxP3-mediated GARP expression is the conversion of tumor-specific Th17 cells to ex-Th17 FoxP3 + cells that show upregulation of surface GARP as a transdifferentiation-associated marker [ 33 ].…”

Section: Garp: Gene and Protein Structurementioning

confidence: 99%

Immunoregulatory functions and the therapeutic implications of GARP-TGF-β in inflammation and cancer

et al. 2018

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GARP (glycoprotein-A repetitions predominant) is a type I transmembrane cell surface docking receptor for latent transforming growth factor-β (TGF-β) that is abundantly expressed on regulatory T lymphocytes and platelets. GARP regulates the availability of membrane-bound latent TGF-β and modulates its activation. For this reason, GARP expression on immune and non-immune cells is involved in maintaining peripheral tolerance. It plays an important role in preventing inflammatory diseases such as allergy and graft versus host disease (GvHD). GARP is also frequently hijacked by cancer cells to promote oncogenesis. This review summarizes the most important features of GARP biology described to date including gene regulation, protein expression and mechanism in activating latent TGF-β, and the function of GARP in regulatory T cell biology and peripheral tolerance, as well as GARP’s increasingly recognized roles in platelet-mediated cancer immune evasion. The promise for GARP-targeted strategy as a novel immunotherapy of cancer is also highlighted.

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Methylation of an intragenic alternative promoter regulates transcription of GARP

Cited by 17 publications

References 33 publications

Identification of chromatin‐accessible domains in non‐alcoholic steatohepatitis‐derived hepatocellular carcinoma

Identification of chromatin‐accessible domains in non‐alcoholic steatohepatitis‐derived hepatocellular carcinoma

B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex

Immunoregulatory functions and the therapeutic implications of GARP-TGF-β in inflammation and cancer

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