A Conserved Noncoding Sequence Can Function as a Spermatocyte-Specific Enhancer and a Bidirectional Promoter for a Ubiquitously Expressed Gene and a Testis-Specific Long Noncoding RNA

Kurihara, Misuzu; Shiraishi, Akira; Satake, Honoo; Kimura, Atsushi P.

A Conserved Noncoding Sequence Can Function as a Spermatocyte-Specific Enhancer and a Bidirectional Promoter for a Ubiquitously Expressed Gene and a Testis-Specific Long Noncoding RNA

Kurihara, Misuzu; Shiraishi, Akira; Satake, Honoo et al.

Journal of Molecular Biology, 2014, 426(17), 3069-3093

Permalink : https://hdl.handle.net/2115/57322

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アクセス権	open access
URI	https://hdl.handle.net/2115/57322
タイトル	A Conserved Noncoding Sequence Can Function as a Spermatocyte-Specific Enhancer and a Bidirectional Promoter for a Ubiquitously Expressed Gene and a Testis-Specific Long Noncoding RNA
著者	Kurihara, Misuzu ; Shiraishi, Akira ; Satake, Honoo ; Kimura, Atsushi P.
著者名 Kurihara, Misuzu
著者名 Shiraishi, Akira
著者名 Satake, Honoo
e-Rad_Researcher 90422005 著者名 Kimura, Atsushi P.
言語	英語
キーワード	Tcam1
	GC-2spd(ts)
	enhancer
	long noncoding RNA
	conserved noncoding sequence
発行日	2014-08-26
出版者	Elsevier
収録物名	Journal of Molecular Biology
巻(号)	426(17)
ページ	3069-3093
抄録	Tissue-specific gene expression is tightly regulated by various elements such as promoters, enhancers, and long noncoding RNAs (IncRNAs). In the present study, we identified a conserved noncoding sequence (CNS1) as a novel enhancer for the spermatocyte-specific mouse testicular cell adhesion molecule 1 (Tcam1) gene. CNS1 was located 3.4 kb upstream of the Tcam1 gene and associated with histone H3K4 mono-methylation in testicular germ cells. By the in vitro reporter gene assay, CNS1 could enhance Tcam1 promoter activity only in GC-2spd(ts) cells, which were derived from mouse spermatocytes. When we integrated the 6.9-kb 5'-flanking sequence of Tcam1 with or without a deletion of CNS1 linked to the enhanced green fluorescent protein gene into the chromatin of GC-2spd(ts) cells, CNS1 significantly enhanced Tcam1 promoter activity. These results indicate that CNS1 could function as a spermatocyte-specific enhancer. Interestingly, CNS1 also showed high bidirectional promoter activity in the reporter assay, and consistent with this, the Smarcd2 gene and IncRNA, designated IncRNA-Tcam1, were transcribed from adjacent regions of CNS1. While Smarcd2 was ubiquitously expressed, IncRNA-Tcam1 expression was restricted to testicular germ cells, although this IncRNA did not participate in Tcam1 activation. Ubiquitous Smarcd2 expression was correlated to CpG hypo-methylation of CNS1 and partially controlled by Sp1. However, for IncRNA-Tcam1 transcription, the strong association with histone acetylation and histone H3K4 tri-methylation also appeared to be required. The present data suggest that CNS1 is a spermatocyte-specific enhancer for the Tcam1 gene and a bidirectional promoter of Smarcd2 and IncRNA-Tcam1.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	(C) 2014 Elsevier Ltd. All rights reserved.
PISSN	0022-2836
EISSN	1089-8638
関連情報	PMID 25020229
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.jmb.2014.06.018