Lower polyunsaturated fatty acid levels and FADS2 expression in adult compared to neonatal keratinocytes are associated with FADS2 promotor hypermethylation.
Lower polyunsaturated fatty acid levels and FADS2 expression in adult compared to neonatal keratinocytes are associated with FADS2 promotor hypermethylation.
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DOI：
10.1016/j.bbrc.2022.02.055
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发表时间：
2022-04-23
影响因子：
3.1
通讯作者：
Griffiths HR
中科院分区：
文献类型：
--
作者：
Pararasa C;Messenger DJ;Barrett KE;Hyliands D;Talbot D;Fowler MI;Kawatra T;Gunn DA;Lim FL;Wainwright LJ;Jenkins G;Griffiths HR
角质形成细胞产生对皮肤屏障至关重要的脂质，然而，关于年龄对这些细胞中脂肪酸（FA）生物合成的影响知之甚少。我们研究了角质形成细胞FA组成，脂质生物合成基因表达，基因启动子甲基化和年龄之间的关系。成人角质形成细胞与新生儿角质形成细胞相比，延长酶（FADS 6和7）和去饱和酶（FADS 1和2）基因的表达较低，并且与成人细胞中n-7、n-9和n-10多不饱和FA的浓度较低相关。与这些发现一致，新生儿角质形成细胞中的瞬时FADS 2敲低模拟了新生儿细胞中的成人角质形成细胞FA谱。对FADS 2基因座（53个基因组位点）的甲基化水平的调查显示，新生儿与成人角质形成细胞中有15个位点存在差异甲基化，其中成人角质形成细胞中的3个高甲基化位点与FADS 2启动子中的SMARCA 4蛋白结合位点重叠。与来自新生儿的角质形成细胞相比，来自成人供体皮肤的原代角质形成细胞合成较少的不饱和脂肪酸。新生角质形成细胞中的FADS 2敲低将细胞脂肪酸组成转换为模拟成人角质形成细胞。在成年角质形成细胞中，FADS 2启动子中的SMARCA 4结合位点是高甲基化的。SMARCA 4结合位点的表观遗传调控可能会影响皮肤细胞中的脂肪酸组成。
Keratinocytes produce lipids that are critical for the skin barrier, however, little is known about the impact of age on fatty acid (FA) biosynthesis in these cells. We have examined the relationship between keratinocyte FA composition, lipid biosynthetic gene expression, gene promoter methylation and age. Expression of elongase (ELOVL6 and 7) and desaturase (FADS1 and 2) genes was lower in adult versus neonatal keratinocytes, and was associated with lower concentrations of n-7, n-9 and n-10 polyunsaturated FA in adult cells. Consistent with these findings, transient FADS2 knockdown in neonatal keratinocytes mimicked the adult keratinocyte FA profile in neonatal cells. Interrogation of methylation levels across the FADS2 locus (53 genomic sites) revealed differential methylation of 15 sites in neonatal versus adult keratinocytes, of which three hypermethylated sites in adult keratinocytes overlapped with a SMARCA4 protein binding site in the FADS2 promoter. Primary keratinocytes from adult donor skin synthesise less unsaturated fatty acids compared to keratinocytes from neonates. FADS2 knockdown in neonatal keratinocytes switches cellular fatty acid composition to mimic adult keratinocytes. In adult keratinocytes, the SMARCA4 binding site in the FADS2 promoter is hypermethylated. Epigenetic regulation at the SMARCA4 binding site may affect fatty acid composition in skin cells.
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影响因子：
3.6
作者：
Qian, Hong;Xu, Xiangru
通讯作者：
Xu, Xiangru
DOI：
10.1093/gerona/glw185
发表时间：
2017-08-01
影响因子：
5.1
作者：
Bacalini, Maria Giulia;Deelen, Joris;Garagnani, Paolo
通讯作者：
Garagnani, Paolo
影响因子：
5.3
作者：
Zampieri, Michele;Ciccarone, Fabio;Caiafa, Paola
通讯作者：
Caiafa, Paola
影响因子：
10.3
作者：
McGrath, J. A.;Robinson, M. K.;Binder, R. L.
通讯作者：
Binder, R. L.
Oreganno 3.0：一种社区驱动的用于策划监管注释的资源。
影响因子：
14.9
作者：
Lesurf R;Cotto KC;Wang G;Griffith M;Kasaian K;Jones SJ;Montgomery SB;Griffith OL;Open Regulatory Annotation Consortium
通讯作者：
Open Regulatory Annotation Consortium