Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TRIM28-dependent SUMOylation protects the adult ovary from the male pathway (ChIP-Seq 2)

ABSTRACT: We study the role of the protein Trim28 in the maintenance of sexual identity of the adult ovary. With the help of conditional knock out (cKO) of Trim28 using the Nr5a1:Cre, we observed that deletion of the Trim28 gene in granulosa cells of the adult ovary induces their transdifferentiation into Sertoli cells, the supporting cell lineage of the testicular seminiferous tubules. FOXL2 expression has disappeared and follicles were completely remodeled into tubular structures with cells that expressed the Sertoli cell markers SOX8, SOX9 and DMRT1. Histological analysis confirmed the progressive reorganization of ovarian follicles into tubular structures and the and the transdifferentiation of granulosa cells by cells with a Sertoli cell morphology. TRIM28 acts as a SUMO-E3 ligase by interacting with the SUMO-E2 conjugating enzyme UBC9 (encoded by the Ube2i gene) via the Plant homeodomain (PHD), and can self-SUMOylate. To study in vivo the role of TRIM28-dependent SUMOylation, we generated a point mutation in exon 13 of mouse Trim28 within the PHD domain of the TRIM28 protein (C651F) that abrogates its SUMO-E3 ligase activity. We generated Trim28Phd/cKO mice (termed PHD mutant). Like in cKO ovaries, FOXL2 expression was undetectable, whereas we observed expression of the Sertoli cell markers SOX9, SOX8 and DMRT1 within structures organized in pseudo-tubules in PHD ovaries. Our results indicate that maintenance of the female pathway in the adult ovary depends on the E3-SUMO ligase activity of TRIM28.

ORGANISM(S): Mus musculus

PROVIDER: GSE166384 | GEO | 2022/05/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

TRIM28-dependent SUMOylation protects the adult ovary from the male pathway (ChIP-Seq 1)

Project description:We study the role of the protein Trim28 in the maintenance of sexual identity of the adult ovary. With the help of conditional knock out (cKO) of Trim28 using the Nr5a1:Cre, we observed that deletion of the Trim28 gene in granulosa cells of the adult ovary induces their transdifferentiation into Sertoli cells, the supporting cell lineage of the testicular seminiferous tubules. FOXL2 expression has disappeared and follicles were completely remodeled into tubular structures with cells that expressed the Sertoli cell markers SOX8, SOX9 and DMRT1. Histological analysis confirmed the progressive reorganization of ovarian follicles into tubular structures and the and the transdifferentiation of granulosa cells by cells with a Sertoli cell morphology.

2022-05-24 | GSE166383 | GEO

TRIM28-dependent SUMOylation protects the adult ovary from the male pathway (RNA-Seq)

2022-05-24 | GSE166382 | GEO

Sexual cell fate reprogramming in the ovary by DMRT1

Project description:Transcription factors related to the insect sex determination gene Doublesex (DMRT proteins) control sex determination and/or sexual differentiation in diverse metazoans. They also are implicated in transitions between sex-determining mechanisms during vertebrate evolution. In mice Dmrt1 is required for male gonadal differentiation in somatic cells and germ cells. DMRT1 also maintains male gonadal sex: its loss, even in adults, can trigger sexual fate reprogramming in which male Sertoli cells transdifferentiate into their female equivalents - granulosa cells - and testicular tissue reorganizes to a more ovarian morphology. Here we use a conditional Dmrt1 transgene to show that Dmrt1 is not only necessary but also sufficient to specify male cell identity in the mouse gonad. DMRT1 expression in the ovary silenced the female sex-maintenance gene Foxl2 and reprogrammed juvenile and adult granulosa cells into Sertoli-like cells, triggering formation of structures resembling male seminiferous tubules. DMRT1 can silence Foxl2 even in the absence of the testis-determining genes Sox8 and Sox9. mRNA profiling found that DMRT1 activates many testicular genes and downregulates ovarian genes and single cell RNA-seq in transdifferentiating cells identified dynamically expressed candidate mediators of this process. Strongly upregulated genes were highly enriched on chromosome X, consistent with sexually antagonistic functions. This study provides an in vivo example of single gene reprogramming of cell sexual identity. Our findings suggest a reconsideration of mechanisms involved in human disorders of sexual development (DSD) and empirically support evolutionary models where loss or gain of Dmrt1 function promotes establishment of new vertebrate sex determination systems. RNA-Seq (3 conditions, 2 replicates per condition) and Single Cell RNA-Seq (68 individual cells and 1 bulk cell sample)

2015-02-27 | E-GEOD-64960 | biostudies-arrayexpress

Sumoylation at Chromatin Governs Coordinated Repression of a Transcriptionnal Program Essential for Cell Growth and Proliferation

Project description:mRNA profiling of WI38 wild-type or overexpressiong the SUMO E3 ligase PIASy in human primary fibroblasts 24h post-infection. The goal of this study is to analyse transcriptional changes in cells over-expressing the SUMO E3 ligase PIASy and to compare them with ChIPseq data for several histones marks and proteins of the SUMO machinery including PIASy

2013-11-25 | E-MEXP-3776 | biostudies-arrayexpress

Testis-to-ovary reprogramming and testis regression after ablation of Sox9 in Sox8-/- mice

Project description:We used two Sertoli-cell-specific Cre lines: Wt1-CreERT2 and Sox9-CreERT2, to induce Sox9 ablation on a Sox8 -/- background in the adult testis. Sox9/8 double KO testes undergo testis-to-ovary genetic reprogramming and Sertoli-to-granulosa cell transdifferentiation.

2016-06-08 | E-MTAB-4572 | biostudies-arrayexpress

In fetal testis, SOX9 acts on transcription and splicing of its targets genes through binding to genomic regions with conserved signatures [RNA-seq]

Project description:In mammals, male fate is under the control of the master transcriptional regulator, SOX9: in its presence, somatic precursor cells of the embryonic gonads differentiate into Sertoli cells, the main organizers of testicular differentiation. Therefore, analyzing target genes of this transcription factor allows understanding mechanisms of cellular commitment at the genomic level. With the use of ChIP-seq in murine and bovine wild-type testes combined with RNAseq from mouse testes lacking SOX9, we identified SOX9 target genes in the mammalian fetal gonad. SOX9 in murine and bovine fetal testes binds to a large set of genes conserved among mammals, including those with well-established roles in testis and ovary development. RNAseq analysis shows that testis and ovary display sex specific RNA splicing and that SOX9 mediates both target gene transcription and differential splicing. Regions bound by SOX9 are predominantly 5’ proximal or intra-genic, and display a specific genomic features that we call "Sertoli cell signatures" or SCS. The SCS is conserved among mammals and comprises multiple binding motifs for the Sertoli reprogramming factors SOX9, GATA4 and DMRT1; indeed, independent DMRT1 ChIP-seq confirms the enrichment of the SCS. Bioinformatic analysis of SCSs regions predicts novel regulatory mechanisms prompting functional validation. For example, we detected SCS in target genes of the nuclear factor TRIM28 and we show experimentally that SOX9 and TRIM28 proteins interact in fetal testis.

2016-12-15 | GSE81489 | GEO

In fetal testis, SOX9 acts on transcription and splicing of its targets genes through binding to genomic regions with conserved signatures [ChIP-seq]

2016-12-15 | GSE81488 | GEO

Sexual cell fate reprogramming in the ovary by DMRT1

2015-02-27 | GSE64960 | GEO

The conserved sex regulator/pioneer factor DMRT1 recruits SOX9 in sexual cell fate reprogramming

Project description:Mammalian sexual development commences when fetal bipotential progenitor cells adopt male Sertoli (in XY) or female granulosa (in XX) gonadal cell fates. Differentiation of these cells involves extensive divergence in chromatin state and gene expression, reflecting distinct roles in sexual differentiation and gametogenesis. Surprisingly, differentiated gonadal cell fates require active maintenance through postnatal life to prevent sexual transdifferentiation and female cell fate can be reprogrammed by ectopic expression of the sex regulator DMRT1. Here we examine how DMRT1 reprograms granulosa cells to Sertoli-like cells in vivo and in culture. We define postnatal granulosa- and Sertoli-biased gene expression programs and identify cell type-biased three-dimensional chromatin contacts and differentially accessible chromatin regions (DARs) associated with differentially expressed genes. Using a conditional transgene we find DMRT1 only partially reprograms the ovarian transcriptome in the absence of SOX9 and its paralog SOX8, indicating that these factors functionally cooperate with DMRT1. ATAC-seq and ChIP-seq show that DMRT1 induces formation of many DARs that it binds with SOX9, and DMRT1 is required for binding of SOX9 at most of these sites. We suggest that DMRT1 can act as a pioneer factor to open chromatin and allow binding of SOX9, which then cooperates with DMRT1 to reprogram sexual cell fate.

2021-05-20 | GSE154484 | GEO

Single cell RNA-seq from Trim28 ovary knockout and wildtype mice ovaries and testis

Project description:Single cell RNA-seq (scRNA-seq) from Trim28 ovary knockout and wildtype mice ovaries and testis to help elucidate the function of Trim28 in the adult mouse ovaries. The analysis revealed that loss of Trim28 in the adult mouse ovaries lead to a transcriptional repogramming of the Granulosa cells towards the Sertoli cell fate. Therefore, Trim28 has a function to maintain the adult ovarian cell identity

2022-05-24 | GSE166444 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data