title: Mechanism of Wnt signaling induced down regulation of mrhl long non-coding RNA in mouse spermatogonial cells.
abstract: Long non coding RNAs (lncRNAs) have emerged as important regulators of various biological processes. LncRNAs also behave as response elements or targets of signaling pathway(s) mediating cellular function. Wnt signaling is important in regulating mammalian spermatogenesis. Mrhl RNA negatively regulates canonical Wnt pathway and gets down regulated upon Wnt signaling activation in mouse spermatogonial cells. Also, mrhl RNA regulates expression of genes pertaining to Wnt pathway and spermatogenesis by binding to chromatin. In the present study, we delineate the detailed molecular mechanism of Wnt signaling induced mrhl RNA down regulation in mouse spermatogonial cells. Mrhl RNA has an independent transcription unit and our various experiments like Chromatin Immunoprecipitation (in cell line as well as mouse testis) and shRNA mediated down regulation convincingly show that β-catenin and TCF4, which are the key effector proteins of the Wnt signaling pathway are required for down regulation of mrhl RNA. We have identified Ctbp1 as the co-repressor and its occupancy on mrhl RNA promoter depends on both β-catenin and TCF4. Upon Wnt signaling activation, Ctbp1 mediated histone repression marks increase at the mrhl RNA promoter. We also demonstrate that Wnt signaling induced mrhl RNA down regulation results in an up regulation of various meiotic differentiation marker genes.
authors.affiliation: From the Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O., Bangalore 560064, India.
authors.forename: Vijay Suresh
authors.initials: VS
authors.lastname: Akhade
authors.affiliation: From the Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O., Bangalore 560064, India.
authors.forename: Shrinivas Nivrutti
authors.initials: SN
authors.lastname: Dighe
authors.affiliation: From the Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O., Bangalore 560064, India.
authors.forename: Shubhangini
authors.initials: S
authors.lastname: Kataruka
authors.affiliation: From the Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O., Bangalore 560064, India mrsrao@jncasr.ac.in.
authors.forename: Manchanahalli R Satyanarayana
authors.initials: MR
authors.lastname: Rao
mesh_terms: D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D001665:Binding Sites; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D056970:Co-Repressor Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D015870:Gene Expression; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics*; D013093:Spermatogonia / Q000166:cytology / Q000378:metabolism*; D000073940:Transcription Factor 4; D014158:Transcription, Genetic; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015415:Biomarkers; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D062085:RNA, Long Noncoding; C090743:Tcf4 protein, mouse; D000073940:Transcription Factor 4; D051176:beta Catenin; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein