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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
Title: | 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 |
Authors: | Kurihara, Misuzu Browse this author | Shiraishi, Akira Browse this author | Satake, Honoo Browse this author | Kimura, Atsushi P. Browse this author →KAKEN DB |
Keywords: | Tcam1 | GC-2spd(ts) | enhancer | long noncoding RNA | conserved noncoding sequence |
Issue Date: | 26-Aug-2014 |
Publisher: | Elsevier |
Journal Title: | Journal of Molecular Biology |
Volume: | 426 |
Issue: | 17 |
Start Page: | 3069 |
End Page: | 3093 |
Publisher DOI: | 10.1016/j.jmb.2014.06.018 |
PMID: | 25020229 |
Abstract: | 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. |
Rights: | (C) 2014 Elsevier Ltd. All rights reserved. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/57322 |
Appears in Collections: | 理学院・理学研究院 (Graduate School of Science / Faculty of Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 木村 敦
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