RRC ID 62881
Author Mayama S, Hamazaki N, Maruyama Y, Matsubara S, Kimura AP.
Title Transcriptional activation of the mouse Scd2 gene by interdependent enhancers and long noncoding RNAs in ovarian granulosa cells.
Journal J Reprod Dev
Abstract Specific gene expression in granulosa cells is key for the function of ovary, but the molecular mechanism of transcriptional activation is not well studied. Here we investigated the regulatory mechanism of the mouse stearoyl-CoA desaturase 2 (Scd2) gene encoding an enzyme for lipid metabolism. Northern blot and in situ hybridization indicated that the mouse Scd2 mRNA was highly expressed in ovarian granulosa cells. We found four conserved noncoding sequences (CNSs) and two long noncoding RNAs (lncRNAs) transcribed from regions upstream of the Scd2 gene as candidates of regulatory elements/factors. These lncRNAs were predominantly transcribed in the opposite direction to Scd2 and localized in nuclei and showed the correlation with Scd2 expression, raising the possibility of their transcriptional regulatory roles. Indeed, knockdown of both lncRNAs, lncRNA-sc1 and lncRNA-sc2, significantly decreased the Scd2 mRNA level in primary granulosa cells. Then, we investigated the histone modification pattern at this locus by a chromatin immunoprecipitation assay, and two CNSs, CNS1 and CNS2, were found to be marked with high levels of histone H3K9/K27 acetylation in primary granulosa cells. By a reporter gene assay, both CNS1 and CNS2 interdependently exhibited enhancer activity for the Scd2 promoter in primary granulosa cells. These data suggest that the mouse Scd2 gene is activated by two lncRNAs and interdependent enhancers in ovarian granulosa cells, which provides a new insight into transcriptional activation in granulosa cells.
Volume 66(5)
Pages 435-444
Published 2020-10-13
DOI 10.1262/jrd.2019-161
PMID 32507774
PMC PMC7593631
MeSH Animals Chromatin Immunoprecipitation Conserved Sequence Enhancer Elements, Genetic Female Gene Expression Profiling Gene Expression Regulation* Genes, Reporter Granulosa Cells / cytology Granulosa Cells / metabolism* Histones / metabolism Humans Mice Mice, Inbred C57BL Oligonucleotides, Antisense / metabolism Ovary / metabolism Promoter Regions, Genetic RNA, Long Noncoding* Stearoyl-CoA Desaturase / genetics* Transcriptional Activation*
IF 1.735
Human and Animal Cells Hepa 1-6(RCB1638)