Dataset Information

Interaction partners with NOP2/Sun RNA methyltransferase 2 (NSUN2) in gallbladder carcinoma

ABSTRACT: Proteins interacting with NSUN2 in gallbladder carcinoma (NOZ cell line)

ORGANISM(S): Homo Sapiens

SUBMITTER: Yingbin Liu

PROVIDER: PXD013152 | iProX | Wed Mar 20 00:00:00 GMT 2019

REPOSITORIES: iProX

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Publications

NOP2/Sun RNA methyltransferase 2 promotes tumor progression via its interacting partner RPL6 in gallbladder carcinoma.

Gao Yuan Y Wang Zheng Z Zhu Yidi Y Zhu Qin Q Yang Yang Y Jin Yunpeng Y Zhang Fei F Jiang Lin L Ye Yuanyuan Y Li Huaifeng H Zhang Yichi Y Liang Haibin H Xiang Shanshan S Miao Huijie H Liu Yingbin Y Hao Yajuan Y

Cancer science 20190923 11

NOP2/Sun domain family, member 2 (NSUN2) is a nuclear RNA methyl-transferase catalyzing 5-methylcytosine formation. Evidence shows that NSUN2 is correlated with cell unlimited proliferation. However, its functional role in gallbladder carcinoma (GBC), which is the most common biliary tract malignancy and has a poor prognosis, remains to be determined. Here we found that NSUN2 was highly expressed in GBC tissues as well as cell lines. NSUN2 silencing repressed GBC cell proliferation and tumorigen ...[more]

PMID: 31487418

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Project description:FOXL2 is a transcription factor essential for female fertility, expressed in somatic cells of the ovary, notably granulosa cells. In the mouse, Foxl2 deletion leads to partial sex reversal postnatally, with mutants developing dysgenic ovaries devoid of oocytes. However, deletion of the gene in 8-week-old females leads to granulosa to Sertoli cell transdifferentiation and gonadal sex reversal. We hypothesise that different outcomes of Foxl2 deletion in embryonic versus adult ovary may depend on a different role played by FOXL2 across ovarian development. Therefore, in this study, we take a multi-omics approach to characterise the dynamics of gene expression and chromatin accessibility changes in purified murine granulosa cells across key developmental stages (E14.5, 1 and 8 weeks). We coupled these analyses with genome wide identification of FOXL2 target genes and on-chromatin interacting partners by ChIP-SICAP to reconstruct the gene regulatory networks underpinned by this essential transcription factor and to discover novel players. We found that, in the embryonic ovary, FOXL2 interacts with factors important for early stages of gonadal development, such as GATA4 and WT1, whilst postnatally it interacts with factors regulating primordial follicle activation, such as NR5A2, and with factors regulating steroidogenesis including AR and ESR2. Integration of chromatin landscape dynamics with gene expression changes and FOXL2 binding sites analysis revealed that its critical role in ovarian cell fate maintenance goes beyond repression of the Sertoli-specific gene Sox9. Our chromatome analysis revealed also that FOXL2 interacts with several proteins involved in chromatin remodelling, DNA repair, splicing and gene repression. We identified a FOXL2 interactor with a role in primordial follicle activation, Ubiquitin specific protease 7 (USP7). We showed that conditional deletion of this gene in granulosa cells leads to a blockage of primordial follicle activation, impairs ovary development and leads to complete sterility. In summary, in this study we identified target genes dynamically regulated by FOXL2 across ovarian development including known and newly identified FOXL2 targets with a role in embryonic ovarian development and folliculogenesis, as well as cofactors that point towards additional roles played by FOXL2 besides transcriptional regulation. This work constitutes a comprehensive resource for exploration of the molecular mechanisms of ovarian development and causes of female infertility.

Dataset Information

Interaction partners with NOP2/Sun RNA methyltransferase 2 (NSUN2) in gallbladder carcinoma

Publications

NOP2/Sun RNA methyltransferase 2 promotes tumor progression via its interacting partner RPL6 in gallbladder carcinoma.

Similar Datasets

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