Suppression of dsRNA response genes and innate immunity following Oct4, Stella, and Nanos2 overexpression in mouse embryonic fibroblasts

Farshchian, Moein; Matin, Maryam Moghaddam; Armant, Olivier; Geerts, Dirk; Dastpak, Mahtab; Nakhaei‐Rad, Saeideh; Tajeran, Massoumeh; Jebelli, Amir; Shahriyari, Mina; Bahrami, Mohsen; Fallah, Ali; Yaghoobi, Vesal; Mirahmadi, Mahdi; Abbaszadegan, Mohammad Reza; Bahrami, Ahmad Reza

doi:10.1016/j.cyto.2018.02.021

Cited by 6 publications

(6 citation statements)

References 28 publications

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“…1b). Such results suggested the potential role of TEs as promoters in mouse tissue development as previously reported [7,[19][20][21][22][23][24][46][47][48][49][50][51]. Approximately 10% of accessible TEs were commonly accessible in all five tissues (Fig.…”

Section: Resultssupporting

confidence: 85%

“…Recent high-throughput sequencing technologies to characterize the transcriptomes and epigenomes of multicellular eukaryotes have revealed the crucial roles of TEs in the evolution of gene regulation. Integration of TEs into host genomes has brought numerous TF binding sites, and such perturbation of the genome interfered with gene regulatory networks and increased the regulatory dynamics of the genome when responding to external stimuli [18][19][20][21][22][23]. Specifically, the intact transcriptional elements of TEs can create novel transcription start sites (TSSs) to initiate transcription in the host genome.…”

Section: Discussionmentioning

confidence: 99%

“…However, mounting evidence suggests that some TEs escape from epigenetic silencing and are actively involved in a diverse array of biological processes (e.g., embryogenesis and carcinogenesis) and can become an essential component (e.g., promoter, enhancer, or insulator) of gene regulatory networks in the host genome [5,[7][8][9][10][13][14][15][16][17]. Specifically, TEs have been found to initiate some genes' transcription, especially for genes involved in immunity or response to external stimuli [18][19][20][21][22][23]. Recent evidence also suggests that TEs are significant contributors to the origin of vertebrate long non-coding RNAs [7,24].…”

Section: Introductionmentioning

confidence: 99%

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Tissue-specific usage of transposable element-derived promoters in mouse development

Miao

Lyu

et al. 2020

Genome Biol

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Background Transposable elements (TEs) are a significant component of eukaryotic genomes and play essential roles in genome evolution. Mounting evidence indicates that TEs are highly transcribed in early embryo development and contribute to distinct biological functions and tissue morphology. Results We examine the epigenetic dynamics of mouse TEs during the development of five tissues: intestine, liver, lung, stomach, and kidney. We found that TEs are associated with over 20% of open chromatin regions during development. Close to half of these accessible TEs are only activated in a single tissue and a specific developmental stage. Most accessible TEs are rodent-specific. Across these five tissues, 453 accessible TEs are found to create the transcription start sites of downstream genes in mouse, including 117 protein-coding genes and 144 lincRNA genes, 93.7% of which are mouse-specific. Species-specific TE-derived transcription start sites are found to drive the expression of tissue-specific genes and change their tissue-specific expression patterns during evolution. Conclusion Our results suggest that TE insertions increase the regulatory potential of the genome, and some TEs have been domesticated to become a crucial component of gene and regulate tissue-specific expression during mouse tissue development.

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Section: Resultssupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tissue-specific usage of transposable element-derived promoters in mouse development

Miao

Lyu

et al. 2020

Genome Biol

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“…8), these data suggest that the two proteins are directly involved in the IFITM1/3 dependent IFNγ response. ISG15 is also a component of an interferon and immune responsive gene cluster that are suppressed by stem cell pluripotent gene product expression [63], suggesting that, like HLA suppression, ISG15 suppression might be co-incident with immune escape. In the case of IFITM1/3 signalling, we do not see defects in 'free' monomeric ISG15 in the double IFITM1/IFITM3 null cells, but reductions in the conjugation of higher molecular mass ISG15ylated adducts (Fig.…”

Section: Discussionmentioning

confidence: 99%

The effects of IFITM1 and IFITM3 gene deletion on IFNγ stimulated protein synthesis

Gómez-Herranz

Nekulova

Faktor

et al. 2019

Cellular Signalling

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A B S T R A C TInterferon-induced transmembrane proteins IFITM1 and IFITM3 (IFITM1/3) play a role in both RNA viral restriction and in human cancer progression. Using immunohistochemical staining of FFPE tissue, we identified subgroups of cervical cancer patients where IFITM1/3 protein expression is inversely related to metastasis. Guide RNA-CAS9 methods were used to develop an isogenic IFITM1/IFITM3 double null cervical cancer model in order to define dominant pathways triggered by presence or absence of IFITM1/3 signalling. A pulse SILAC methodology identified IRF1, HLA-B, and ISG15 as the most dominating IFNγ inducible proteins whose synthesis was attenuated in the IFITM1/IFITM3 double-null cells. Conversely, SWATH-IP mass spectrometry of ectopically expressed SBP-tagged IFITM1 identified ISG15 and HLA-B as dominant co-associated proteins. ISG15ylation was attenuated in IFNγ treated IFITM1/IFITM3 double-null cells. Proximity ligation assays indicated that HLA-B can interact with IFITM1/3 proteins in parental SiHa cells. Cell surface expression of HLA-B was attenuated in IFNγ treated IFITM1/IFITM3 double-null cells. SWATH-MS proteomic screens in cells treated with IFITM1-targeted siRNA cells resulted in the attenuation of an interferon regulated protein subpopulation including MHC Class I molecules as well as IFITM3, STAT1, B2M, and ISG15. These data have implications for the function of IFITM1/3 in mediating IFNγ stimulated protein synthesis including ISG15ylation and MHC Class I production in cancer cells. The data together suggest that pro-metastatic growth associated with IFITM1/3 negative cervical cancers relates to attenuated expression of MHC Class I molecules that would support tumor immune escape.Abbreviations: B2M, beta-2-microglobulin; FASP, filter-aided sample preparation; FA, formic acid; HLA, human leucocyte antigen; IFN, interferon; IFITM1/3, interferon-induced transmembrane receptors 1 and 3; ISG15, interferon-stimulated gene 15; IRF1, interferon regulatory factor 1; MHC, major histocompatibility complex; MS, mass spectrometry; NMWCO, nominal molecular weight cut-off; PBS, phosphate-buffered saline; PLA, proximity ligation assay; RT, room temperature; SWATH-IP, SWATH immunoprecipitation; SBP, twin streptavidin binding protein; UPLC, ultra performance liquid chromatography ⁎ Corresponding authors at

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“…The Dppa3-positive neighboring ACD and intraembryonic posterior primitive streak develop into different styles of somatic cells that encompass derivatives of the three primary germ layers. 46 All of these suggested that Dppa3 has critical roles in PGC development. 40 At the process of germ cell development, the PGCs express different genes at different time points and undergo specific epigenetic remodeling.…”

Section: Dppa3 In Pgc Developmentmentioning

confidence: 99%

Dppa3 in pluripotency maintenance of ES cells and early embryogenesis

Zhao

Liu

et al. 2018

J of Cellular Biochemistry

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Embryonic development is precisely regulated by a network of signal pathways and specific genes. Dppa3 (also known as Pgc7 or Stella) plays an important role in early embryonic development during the cleavage stage as a maternal effect gene. Dppa3 expresses in many species, and its homologous gene in human and rat genomes is located at the same chromosomal regions and have the same exon‐intron structure. However, unlike mouse embryonic stem (ES) cells, in which the Dppa3 promoter maintains hypomethylation that allows a high transcription level, the DPPA3 promoter region in human ES cells is methylated, much like that of mouse epiblast stem cell. Dppa3 is essential for early embryogenesis and pluripotency maintenance; however, the precise mechanism and downstream passage remains unknown. In this review, we will summarize some important functions of Dppa3 in early embryogenesis and pluripotency maintenance of mouse ES cells.

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Suppression of dsRNA response genes and innate immunity following Oct4, Stella, and Nanos2 overexpression in mouse embryonic fibroblasts

Cited by 6 publications

References 28 publications

Tissue-specific usage of transposable element-derived promoters in mouse development

Tissue-specific usage of transposable element-derived promoters in mouse development

The effects of IFITM1 and IFITM3 gene deletion on IFNγ stimulated protein synthesis

Dppa3 in pluripotency maintenance of ES cells and early embryogenesis

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