4.6 Article

A dual enhancer-silencer element, DES-K16, in mouse spermatocyte-derived GC-2spd(ts) cells

期刊

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2020.10.049

关键词

Dual enhancer-silencer; Multifunctional genome; Spermatocyte; GC-2spd(ts) cell; ChIP-sequencing; Histone modification

资金

  1. KAKENHI [15H04317, 20H03285]
  2. Japan Society for the Promotion of Science and Suhara Memorial foundation
  3. Grants-in-Aid for Scientific Research [20H03285, 15H04317] Funding Source: KAKEN

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The study identified a genomic region with dual enhancer and silencer functions, showing the ability to activate and suppress gene expression in a single cell type. This new finding expands our understanding of the multifunctionality of the genome.
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.

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