The Kat in the HAT: The Histone Acetyl Transferase Kat6b (MYST4) Is Downregulated in Murine Macrophages in Response to LPS.
The Kat in the HAT: The Histone Acetyl Transferase Kat6b (MYST4) Is Downregulated in Murine Macrophages in Response to LPS.
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DOI：
10.1155/2018/7852742
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发表时间：
2018
影响因子：
4.6
通讯作者：
Leibovich SJ
中科院分区：
文献类型：
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作者：
Shukla S;Levine C;Sripathi RP;Elson G;Lutz CS;Leibovich SJ
表观遗传调节剂，包括组蛋白甲基化酶、脱甲基酶和脱乙酰酶，先前已经涉及经典和替代巨噬细胞活化途径的调节。在这项研究中，我们发现，组蛋白乙酰转移酶（HAT）Kat 6 B（MYST 4）在巨噬细胞中被脂多糖（LPS）（M1激活）强烈抑制（>80%），而Kat 6A，其在MOZ/MORF复合物中的伴侣，则被上调。LPS与腺苷受体激动剂NECA（M2 d激活）一起不会改变这种表达模式。尽管观察到miR-487 b（Kat 6 B表达的推定调节剂）被LPS轻度刺激，但被LPS/NECA强烈抑制。HAT的MYST家族的其他成员（Kat 5、Kat 7和Kat 8）不受LPS处理的影响。使用pLightswitch 3′UTR报告质粒，发现Kat 6 b 3′UTR中的miR-487 b结合位点在LPS介导的Kat 6 B表达抑制中起作用，但其他尚未鉴定的因素也参与其中。由于Kat 6 B是一种HAT，具有通过其对染色质可及性的影响来调节基因表达的潜力，因此我们正在继续研究这种表观遗传调节剂在巨噬细胞活化途径中的潜在作用。
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.
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影响因子：
4.6
作者：
Kapellos TS;Iqbal AJ
通讯作者：
Iqbal AJ
影响因子：
30.5
作者：
通讯作者：
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影响因子：
6
作者：
Grinberg, Stan;Hasko, Gyorgy;Leibovich, Samuel Joseph
通讯作者：
Leibovich, Samuel Joseph
影响因子：
15.9
作者：
Kraft, Michael;Cirstea, Ion Cristian;Thiel, Christian Thomas
通讯作者：
Thiel, Christian Thomas
影响因子：
16.8
作者：
通讯作者：
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