A dual enhancer-silencer element, DES-K16, in mouse spermatocyte-derived GC-2spd(ts) cells
A dual enhancer-silencer element, DES-K16, in mouse spermatocyte-derived GC-2spd(ts) cells
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DOI：
10.1016/j.bbrc.2020.10.049
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发表时间：
2021-01-01
影响因子：
3.1
通讯作者：
Kimura, Atsushi P.
中科院分区：
文献类型：
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作者：
Bandara, Thusitha A. M. K.;Otsuka, Kai;Kimura, Atsushi P.
基因组的多功能性在不同物种的某些位点被提出，但还没有得到很好的理解。在这里，我们确定了一个DES-K16区域的Kctd 16基因的内含子作为染色质高度标记的表观遗传修饰的增强子（H3 K4 me 1和H3 K27 ac）和沉默（H3 K27 me 3）在小鼠精母细胞。体外报告基因分析表明，DES-K16在精母细胞来源的GC-2spd（ts）和肝癌来源的Hepa 1 -6细胞中表现出显著的增强子活性，并且在GC-2spd（ts）细胞中该序列的缺失分别导致Yipf 5和Kctd 16表达的降低和升高。这与睾丸发育过程中初级精母细胞中Yipf 5和Kctd 16表达的增加和减少是一致的。虽然已知的双增强子沉默剂在不同的组织中发挥每种活性，但我们的数据表明，DES-K16在单细胞类型GC-2spd（ts）细胞中同时起增强子和沉默剂的作用。这是第一个报告的双重增强子沉默元件，激活和抑制基因表达在一个单一的细胞类型。(C)2020爱思唯尔公司All rights reserved.
The multifunctionality of genome is suggested at some loci in different species but not well understood. Here we identified a DES-K16 region in an intron of the Kctd16 gene as the chromatin highly marked with epigenetic modifications of both enhancers (H3K4me1 and H3K27ac) and silencers (H3K27me3) in mouse spermatocytes. In vitro reporter gene assay demonstrated that DES-K16 exhibited significant enhancer activity in spermatocyte-derived GC-2spd(ts) and hepatic tumor-derived Hepa1-6 cells, and a deletion of this sequence in GC-2spd(ts) cells resulted in a decrease and increase of Yipf5 and Kctd16 expression, respectively. This was consistent with increased and decreased expression of Yipf5 and Kctd16, respectively, in primary spermatocytes during testis development. While known dual enhancer silencers exert each activity in different tissues, our data suggest that DES-K16 functions as both enhancer and silencer in a single cell type, GC-2spd(ts) cells. This is the first report on a dual enhancer-silencer element which activates and suppresses gene expression in a single cell type. (C) 2020 Elsevier Inc. All rights reserved.