Cargando…
Novel Insights into the Downstream Pathways and Targets Controlled by Transcription Factors CREM in the Testis
The essential role of the Crem gene in normal sperm development is widely accepted and is confirmed by azoospermia in male mice lacking the Crem gene. The exact number of genes affected by Crem absence is not known, however a large difference has been observed recently between the estimated number o...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285179/ https://www.ncbi.nlm.nih.gov/pubmed/22384077 http://dx.doi.org/10.1371/journal.pone.0031798 |
_version_ | 1782224466578767872 |
---|---|
author | Kosir, Rok Juvan, Peter Perse, Martina Budefeld, Tomaz Majdic, Gregor Fink, Martina Sassone-Corsi, Paolo Rozman, Damjana |
author_facet | Kosir, Rok Juvan, Peter Perse, Martina Budefeld, Tomaz Majdic, Gregor Fink, Martina Sassone-Corsi, Paolo Rozman, Damjana |
author_sort | Kosir, Rok |
collection | PubMed |
description | The essential role of the Crem gene in normal sperm development is widely accepted and is confirmed by azoospermia in male mice lacking the Crem gene. The exact number of genes affected by Crem absence is not known, however a large difference has been observed recently between the estimated number of differentially expressed genes found in Crem knock-out (KO) mice compared to the number of gene loci bound by CREM. We therefore re-examined global gene expression in male mice lacking the Crem gene using whole genome transcriptome analysis with Affymetrix microarrays and compared the lists of differentially expressed genes from Crem−/− mice to a dataset of genes where binding of CREM was determined by Chip-seq. We determined the global effect of CREM on spermatogenesis as well as distinguished between primary and secondary effects of the CREM absence. We demonstrated that the absence of Crem deregulates over 4700 genes in KO testis. Among them are 101 genes associated with spermatogenesis 41 of which are bound by CREM and are deregulated in Crem KO testis. Absence of several of these genes in mouse models has proven their importance for normal spermatogenesis and male fertility. Our study showed that the absence of Crem plays a more important role on different aspects of spermatogenesis as estimated previously, with its impact ranging from apoptosis induction to deregulation of major circadian clock genes, steroidogenesis and the cell-cell junction dynamics. Several new genes important for normal spermatogenesis and fertility are down-regulated in KO testis and are therefore possible novel targets of CREM. |
format | Online Article Text |
id | pubmed-3285179 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32851792012-03-01 Novel Insights into the Downstream Pathways and Targets Controlled by Transcription Factors CREM in the Testis Kosir, Rok Juvan, Peter Perse, Martina Budefeld, Tomaz Majdic, Gregor Fink, Martina Sassone-Corsi, Paolo Rozman, Damjana PLoS One Research Article The essential role of the Crem gene in normal sperm development is widely accepted and is confirmed by azoospermia in male mice lacking the Crem gene. The exact number of genes affected by Crem absence is not known, however a large difference has been observed recently between the estimated number of differentially expressed genes found in Crem knock-out (KO) mice compared to the number of gene loci bound by CREM. We therefore re-examined global gene expression in male mice lacking the Crem gene using whole genome transcriptome analysis with Affymetrix microarrays and compared the lists of differentially expressed genes from Crem−/− mice to a dataset of genes where binding of CREM was determined by Chip-seq. We determined the global effect of CREM on spermatogenesis as well as distinguished between primary and secondary effects of the CREM absence. We demonstrated that the absence of Crem deregulates over 4700 genes in KO testis. Among them are 101 genes associated with spermatogenesis 41 of which are bound by CREM and are deregulated in Crem KO testis. Absence of several of these genes in mouse models has proven their importance for normal spermatogenesis and male fertility. Our study showed that the absence of Crem plays a more important role on different aspects of spermatogenesis as estimated previously, with its impact ranging from apoptosis induction to deregulation of major circadian clock genes, steroidogenesis and the cell-cell junction dynamics. Several new genes important for normal spermatogenesis and fertility are down-regulated in KO testis and are therefore possible novel targets of CREM. Public Library of Science 2012-02-22 /pmc/articles/PMC3285179/ /pubmed/22384077 http://dx.doi.org/10.1371/journal.pone.0031798 Text en Kosir et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kosir, Rok Juvan, Peter Perse, Martina Budefeld, Tomaz Majdic, Gregor Fink, Martina Sassone-Corsi, Paolo Rozman, Damjana Novel Insights into the Downstream Pathways and Targets Controlled by Transcription Factors CREM in the Testis |
title | Novel Insights into the Downstream Pathways and Targets Controlled by Transcription Factors CREM in the Testis |
title_full | Novel Insights into the Downstream Pathways and Targets Controlled by Transcription Factors CREM in the Testis |
title_fullStr | Novel Insights into the Downstream Pathways and Targets Controlled by Transcription Factors CREM in the Testis |
title_full_unstemmed | Novel Insights into the Downstream Pathways and Targets Controlled by Transcription Factors CREM in the Testis |
title_short | Novel Insights into the Downstream Pathways and Targets Controlled by Transcription Factors CREM in the Testis |
title_sort | novel insights into the downstream pathways and targets controlled by transcription factors crem in the testis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285179/ https://www.ncbi.nlm.nih.gov/pubmed/22384077 http://dx.doi.org/10.1371/journal.pone.0031798 |
work_keys_str_mv | AT kosirrok novelinsightsintothedownstreampathwaysandtargetscontrolledbytranscriptionfactorscreminthetestis AT juvanpeter novelinsightsintothedownstreampathwaysandtargetscontrolledbytranscriptionfactorscreminthetestis AT persemartina novelinsightsintothedownstreampathwaysandtargetscontrolledbytranscriptionfactorscreminthetestis AT budefeldtomaz novelinsightsintothedownstreampathwaysandtargetscontrolledbytranscriptionfactorscreminthetestis AT majdicgregor novelinsightsintothedownstreampathwaysandtargetscontrolledbytranscriptionfactorscreminthetestis AT finkmartina novelinsightsintothedownstreampathwaysandtargetscontrolledbytranscriptionfactorscreminthetestis AT sassonecorsipaolo novelinsightsintothedownstreampathwaysandtargetscontrolledbytranscriptionfactorscreminthetestis AT rozmandamjana novelinsightsintothedownstreampathwaysandtargetscontrolledbytranscriptionfactorscreminthetestis |