Temporal Control of the TGF-β Signaling Network by Mouse ESC MicroRNA Targets of Different Affinities

Kelly, Timothy; Brümmer, Anneke; Hooshdaran, Nima; Tariveranmoshabad, Mito; Zamudio, Jesse R.

doi:10.1016/j.celrep.2019.10.109

Cited by 14 publications

(16 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further, the differential H3K27me3 occupancy at Ago2&1_KO specifically up-and downregulated genes seemed to be rather correlating with the loss of AGO proteins and not due to a miRNA-mediated regulation, as miRNA target genes (Schäfer et al, 2021) are mainly more enriched in active histone marks than H3K27me3 (Fig 2A). Noticeably, recent results have linked AGO2 with H3K27me3 by showing a reduction of H3K27me3 at certain target loci upon Ago2 depletion in mESCs (Kelly et al, 2019). To determine whether the combined loss of AGO2&1 affects H3K27me3 levels and gene expression, we first measured and compared the global levels of several histone marks in Ago2&1_KO mESCs and WT mESCs by Western Blotting (WB) (Fig 2B).…”

Section: Combined Loss Of Ago2and1 In Mescs Causes Global Loss Of H3k27me3mentioning

confidence: 99%

ARGONAUTE proteins regulate a specific network of genes through KLF4 in mouse embryonic stem cells

Mueller

Schaefer

Faeh³

et al. 2021

Preprint

View full text Add to dashboard Cite

The Argonaute proteins (AGO) are well-known for their essential role in post-transcriptional gene silencing in the microRNA (miRNA) pathway. Only two AGOs are expressed in mouse embryonic stem cells (mESCs). The transcriptome of Ago mutant mESCs revealed a large and specific set of differentially expressed genes (DEGs), compared to other miRNA biogenesis factor mutant cells, suggesting additional functions for AGOs. Integration of Ago DEGs with ENCODE histone modification data of WT mESCs revealed a correlation with H3K27me3 chromatin mark. We validated experimentally this result and observed a global loss of H3K27me3, which was only partially explaining the DEGs observed in Ago mutant cells. By integrating chromatin accessibility data in conjunction with the prediction of transcription factor (TF) binding sites, we identified differential binding for five TFs, including KLF4 as a key modulator of more than half of the specific DEGs in the absence of AGO proteins. Our findings illustrate that in addition to chromatin state, information about transcription factor binding is more revelatory in understanding the multi-layered mechanism adopted by cells to regulate gene expression.

show abstract

Section: Combined Loss Of Ago2and1 In Mescs Causes Global Loss Of H3k27me3mentioning

confidence: 99%

ARGONAUTE proteins regulate a specific network of genes through KLF4 in mouse embryonic stem cells

Mueller

Schaefer

Faeh³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Ago1-depletion affects the distribution of H3K9me3 and HP1α at pericentromeric regions Only the H3K27me3 heterochromatin mark, but not H3K9me3, was previously observed to be strongly down-regulated in Argonaute mutant mESCs (Kelly et al, 2019;Mueller et al, 2021 Preprint). Heterochromatin is localized to specific nuclear territories in mammalian cells (Akhtar & Gasser, 2007;Solovei et al, 2009).…”

Section: Resultsmentioning

confidence: 97%

AGO1 regulates pericentromeric regions in mouse embryonic stem cells

Müller

Fäh²,

Schaefer

et al. 2022

Life Sci. Alliance

View full text Add to dashboard Cite

Argonaute proteins (AGOs), which play an essential role in cytosolic post-transcriptional gene silencing, have been also reported to function in nuclear processes like transcriptional activation or repression, alternative splicing and, chromatin organization. As most of these studies have been conducted in human cancer cell lines, the relevance of AGOs nuclear functions in the context of mouse early embryonic development remains uninvestigated. Here, we examined a possible role of the AGO1 protein on the distribution of constitutive heterochromatin in mouse embryonic stem cells (mESCs). We observed a specific redistribution of the repressive histone mark H3K9me3 and the heterochromatin protein HP1α, away from pericentromeric regions upon Ago1 depletion. Furthermore, we demonstrated that major satellite transcripts are strongly up-regulated in Ago1_KO mESCs and that their levels are partially restored upon AGO1 rescue. We also observed a similar redistribution of H3K9me3 and HP1α in Drosha_KO mESCs, suggesting a role for microRNAs (miRNAs) in the regulation of heterochromatin distribution in mESCs. Finally, we showed that specific miRNAs with complementarity to major satellites can partially regulate the expression of these transcripts.

show abstract

“…MicroRNAs (miRNAs) are ~20 nucleotide conserved non-coding RNAs that function as posttranscriptional regulators capable of binding to the 3'-untranslated region (UTR) of target mRNAs to suppress their expression [10,11]. In the context of LSCC, many researchers have identi ed roles for these non-coding RNAs as regulators of cancer onset and progression [12].…”

Section: Introductionmentioning

confidence: 99%

YBX1 promotes laryngeal squamous cell carcinoma progression via activating MAPK/ERK signaling as a target of miR-382-5p

Zeng¹,

Pan²,

Luo

et al. 2021

Preprint

View full text Add to dashboard Cite

Background. Y-box binding protein-1 (YBX1) influences the onset and progression of laryngeal squamous cell carcinoma (LSCC) remains unknown. The present study therefore sought to explore the mechanistic role of YBX1 in LSCC. Methods.Analyses of the Gene Expression Omnibus (GEO) database and associated bioinformatics analyses revealed that YBX1 was upregulated in LSCC, and we further confirmed this result using primary LSCC patient samples. We additionally explored the impact of siRNA-mediated YBX1 knockdown on LSCC cell proliferation, migration, and invasion using CCK8, wound healing, and Transwell assays. We then conducted interrogated miRNA databases and conducted subsequent luciferase reporter assays to confirm that miR-382-5p binds to YBX1. Additional studies of the mechanisms downstream of this miR-382-5p/YBX1 axis focused on detecting the expression of mitogen-activated protein kinase (MAPK)/extracellular regulated kinase (ERK) signaling-related genes via qPCR and Western blotting. Results.We detected significant upregulation of YBX1 in LSCC tumors that was significantly correlated with advanced TNM stage and poor patient prognosis. Knockdown of YBX1 markedly impaired the proliferative, invasive, and migratory activity of Tu212 cells in vitro. From a mechanistic perspective, miR-382-5p was found to bind to the YBX1 3’-untranslated region and to thereby inhibit LSCC progression. We further confirmed that miR-382-5p negatively regulated YBX1 to inhibit proliferation via the MAPK/ ERK signaling axis in LSCC. Conclusion.Together, our results indicated that YBX1 is an important promoter of LSCC progression, and that miR-382-5p can suppress YBX1 expression and inactivate MAPK/ERK signaling. These findings may thus highlight novel and promising prognostic and therapeutic targets in the context of LSCC.

show abstract

Temporal Control of the TGF-β Signaling Network by Mouse ESC MicroRNA Targets of Different Affinities

Cited by 14 publications

References 45 publications

ARGONAUTE proteins regulate a specific network of genes through KLF4 in mouse embryonic stem cells

ARGONAUTE proteins regulate a specific network of genes through KLF4 in mouse embryonic stem cells

AGO1 regulates pericentromeric regions in mouse embryonic stem cells

YBX1 promotes laryngeal squamous cell carcinoma progression via activating MAPK/ERK signaling as a target of miR-382-5p

Contact Info

Product

Resources

About