The Kat in the HAT: The Histone Acetyl Transferase Kat6b (MYST4) Is Downregulated in Murine Macrophages in Response to LPS
Epigenetic modulators, including histone methylases, demethylases, and deacetylases, have been implicated previously in the regulation of classical and alternative macrophage activation pathways. In this study, we show that the histone acetyl transferase (HAT) Kat6B (MYST4) is strongly suppressed (&...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2018/7852742 |
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| author | Smita Shukla Carly Levine Roopa Payanur Sripathi Genie Elson Carol Susan Lutz Samuel Joseph Leibovich |
| author_facet | Smita Shukla Carly Levine Roopa Payanur Sripathi Genie Elson Carol Susan Lutz Samuel Joseph Leibovich |
| author_sort | Smita Shukla |
| collection | DOAJ |
| description | Epigenetic modulators, including histone methylases, demethylases, and deacetylases, have been implicated previously in the regulation of classical and alternative macrophage activation pathways. In this study, we show that the histone acetyl transferase (HAT) Kat6B (MYST4) is strongly suppressed (>80%) in macrophages by lipopolysaccharide (LPS) (M1 activation), while Kat6A, its partner in the MOZ/MORF complex, is reciprocally upregulated. This pattern of expression is not altered by LPS together with the adenosine receptor agonist NECA (M2d activation). This is despite the observation that miR-487b, a putative regulator of Kat6B expression, is mildly stimulated by LPS, but strongly suppressed by LPS/NECA. Other members of the MYST family of HATs (Kat5, Kat7, and Kat8) are unaffected by LPS treatment. Using the pLightswitch 3′UTR reporter plasmid, the miR-487b binding site in the Kat6b 3′UTR was found to play a role in the LPS-mediated suppression of Kat6B expression, but other as-yet unidentified factors are also involved. As Kat6B is a HAT that has the potential to modulate gene expression by its effects on chromatin accessibility, we are continuing our studies into the potential roles of this epigenetic modulator in macrophage activation pathways. |
| format | Article |
| id | doaj-art-3976549c36b64d049a8c9650ced073c5 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-3976549c36b64d049a8c9650ced073c52025-02-03T05:50:33ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/78527427852742The Kat in the HAT: The Histone Acetyl Transferase Kat6b (MYST4) Is Downregulated in Murine Macrophages in Response to LPSSmita Shukla0Carly Levine1Roopa Payanur Sripathi2Genie Elson3Carol Susan Lutz4Samuel Joseph Leibovich5Department of Cell Biology & Molecular Medicine, Rutgers Biomedical & Health Sciences, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USADepartment of Cell Biology & Molecular Medicine, Rutgers Biomedical & Health Sciences, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USAThe School of Graduate Studies, Rutgers Biomedical & Health Sciences, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USADepartment of Cell Biology & Molecular Medicine, Rutgers Biomedical & Health Sciences, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USAThe School of Graduate Studies, Rutgers Biomedical & Health Sciences, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USADepartment of Cell Biology & Molecular Medicine, Rutgers Biomedical & Health Sciences, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USAEpigenetic modulators, including histone methylases, demethylases, and deacetylases, have been implicated previously in the regulation of classical and alternative macrophage activation pathways. In this study, we show that the histone acetyl transferase (HAT) Kat6B (MYST4) is strongly suppressed (>80%) in macrophages by lipopolysaccharide (LPS) (M1 activation), while Kat6A, its partner in the MOZ/MORF complex, is reciprocally upregulated. This pattern of expression is not altered by LPS together with the adenosine receptor agonist NECA (M2d activation). This is despite the observation that miR-487b, a putative regulator of Kat6B expression, is mildly stimulated by LPS, but strongly suppressed by LPS/NECA. Other members of the MYST family of HATs (Kat5, Kat7, and Kat8) are unaffected by LPS treatment. Using the pLightswitch 3′UTR reporter plasmid, the miR-487b binding site in the Kat6b 3′UTR was found to play a role in the LPS-mediated suppression of Kat6B expression, but other as-yet unidentified factors are also involved. As Kat6B is a HAT that has the potential to modulate gene expression by its effects on chromatin accessibility, we are continuing our studies into the potential roles of this epigenetic modulator in macrophage activation pathways.http://dx.doi.org/10.1155/2018/7852742 |
| spellingShingle | Smita Shukla Carly Levine Roopa Payanur Sripathi Genie Elson Carol Susan Lutz Samuel Joseph Leibovich The Kat in the HAT: The Histone Acetyl Transferase Kat6b (MYST4) Is Downregulated in Murine Macrophages in Response to LPS Mediators of Inflammation |
| title | The Kat in the HAT: The Histone Acetyl Transferase Kat6b (MYST4) Is Downregulated in Murine Macrophages in Response to LPS |
| title_full | The Kat in the HAT: The Histone Acetyl Transferase Kat6b (MYST4) Is Downregulated in Murine Macrophages in Response to LPS |
| title_fullStr | The Kat in the HAT: The Histone Acetyl Transferase Kat6b (MYST4) Is Downregulated in Murine Macrophages in Response to LPS |
| title_full_unstemmed | The Kat in the HAT: The Histone Acetyl Transferase Kat6b (MYST4) Is Downregulated in Murine Macrophages in Response to LPS |
| title_short | The Kat in the HAT: The Histone Acetyl Transferase Kat6b (MYST4) Is Downregulated in Murine Macrophages in Response to LPS |
| title_sort | kat in the hat the histone acetyl transferase kat6b myst4 is downregulated in murine macrophages in response to lps |
| url | http://dx.doi.org/10.1155/2018/7852742 |
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