scholarly journals Stem cell specific interferon stimulated gene expression is regulated by the formative pluripotency network through IRF1

2021 ◽  
Author(s):  
Merrit Romeike ◽  
Stephanie Spach ◽  
Marie Huber ◽  
Songjie Feng ◽  
Gintautas Vainorius ◽  
...  
Keyword(s):  
Stem Cells ◽  
Innate Immunity ◽  
Regulatory Factor ◽  
Interferon Stimulated Genes ◽  
Interferon Regulatory Factor 1 ◽  
Immunity Genes ◽  
Pluripotency Gene ◽  
Gene Regulatory ◽  
Response Expression ◽  
External Stimuli

Stem cells intrinsically express a subset of genes which are normally associated with interferon stimulation, and thus the innate immunity response. Expression of these interferon stimulated genes (ISG) in stem cells is independent of external stimuli such as viral infection. Here we show that the interferon regulatory factor 1, Irf1, is directly controlled by the murine formative pluripotency gene regulatory network and therefore upregulated in the transition from naive to formative pluripotency. IRF1 in turn binds to regulatory regions of a conserved set of ISGs and is required for their faithful expression in formative pluripotent cells. IRF1 also binds to an enhancer of the formative pluripotency transcription factor Oct6 and is partially required for upregulation of Oct6. IRF1 therefore acts as a link between the formative pluripotency network and the regulation of innate immunity genes in formative pluripotency.

scholarly journals BAF Complex in Embryonic Stem Cells and Early Embryonic Development

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Heyao Zhang ◽  
Xuepeng Wang ◽  
Jingsheng Li ◽  
Ronghua Shi ◽  
Ying Ye
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Development ◽  
Embryonic Stem ◽  
Early Embryonic Development ◽  
Mouse Escs ◽  
Baf Complex ◽  
Pluripotency Gene ◽  
Chromatin Remodeling Complexes ◽  
Gene Regulatory

Embryonic stem cells (ESCs) can self-renew indefinitely and maintain their pluripotency status. The pluripotency gene regulatory network is critical in controlling these properties and particularly chromatin remodeling complexes. In this review, we summarize the research progresses of the functional and mechanistic studies of BAF complex in mouse ESCs and early embryonic development. A discussion of the mechanistic bases underlying the distinct phenotypes upon the deletion of different BAF subunits in ESCs and embryos will be highlighted.

scholarly journals Histone demethylase complexes KDM3A and KDM3B cooperate with OCT4/SOX2 to construct pluripotency gene regulatory network

2020 ◽  
Author(s):  
Zhenshuo Zhu ◽  
Xiaolong Wu ◽  
Qun Li ◽  
Juqing Zhang ◽  
Shuai Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Regulatory Network ◽  
Pluripotent Stem Cells ◽  
Regulatory Network ◽  
Dynamic Change ◽  
Histone Demethylase ◽  
H3k9 Methylation ◽  
Pluripotent State ◽  
Pluripotency Gene ◽  
Gene Regulatory

AbstractThe pluripotency gene regulatory network of porcine-induced pluripotent stem cells (piPSCs), especially in epigenetics, remains elusive. To determine this biological function of epigenetics, we cultured piPSCs in different culture conditions. We found that activation of pluripotent gene- and pluripotency-related pathways requires the erasure of H3K9 methylation modification which was further influenced by mouse embryonic fibroblast (MEF) served feeder. By dissecting the dynamic change of H3K9 methylation during loss of pluripotency, we demonstrated that the H3K9 demethylases KDM3A and KDM3B regulated global H3K9me2/me3 level and that their co-depletion led to the collapse of the pluripotency gene regulatory network. Immunoprecipitation-mass spectrometry (IP-MS) provided evidence that KDM3A and KDM3B formed a complex to perform H3K9 demethylation. The genome-wide regulation analysis revealed that OCT4 (O) and SOX2 (S), the core pluripotency transcriptional activators, maintained the pluripotent state of piPSCs depending on the H3K9 hypomethylation. Further investigation revealed that O/S cooperating with histone demethylase complex containing KDM3A and KDM3B promoted pluripotency genes expression to maintain the pluripotent state of piPSCs. Together, these data offer a unique insight into the epigenetic pluripotency network of piPSCs.SummaryErasure of H3K9 methylation in porcine pluripotent stem cells depends on the complex of transcription factors OCT4/SOX2 and histone demethylase KDM3A/KDM3B.

scholarly journals Analysis of stop-gain and frameshift variants in human innate immunity genes

2014 ◽  
Author(s):  
Antonio Rausell ◽  
Pejman Mohammadi ◽  
Paul J McLaren ◽  
Ioannis Xenarios ◽  
Jacques Fellay ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Classification Scheme ◽  
Individual Variability ◽  
Loss Of Function ◽  
Sequencing Project ◽  
Interferon Stimulated Genes ◽  
Pathogenic Variants ◽  
Gene Level ◽  
Immunity Genes ◽  
Response Current

Loss-of-function variants in innate immunity genes are associated with Mendelian disorders in the form of primary immunodeficiencies. Recent resequencing projects report that stop-gains and frameshifts are collectively prevalent in humans and could be responsible for some of the inter-individual variability in innate immune response. Current computational approaches evaluating loss-of-function in genes carrying these variants rely on gene-level characteristics such as evolutionary conservation and functional redundancy across the genome. However, innate immunity genes represent a particular case because they are more likely to be under positive selection and duplicated. To create a ranking of severity that would be applicable to the innate immunity genes we first evaluated 17764 stop-gain and 13915 frameshift variants from the NHLBI Exome Sequencing Project and 1000 Genomes Project. Sequence-based features such as loss of functional domains, isoform-specific truncation and non-sense mediated decay were found to correlate with variant allele frequency and validated with gene expression data. We integrated these features in a Bayesian classification scheme and benchmarked its use in predicting pathogenic variants against OMIM disease stop-gains and frameshifts. The classification scheme was applied in the assessment of 335 stop-gains and 236 frameshifts affecting 227 interferon-stimulated genes. The sequence-based score ranks variants in innate immunity genes according to their potential to cause disease, and complements existing gene-based pathogenicity scores.

Myelin Gene Regulatory Factor Is a Critical Transcriptional Regulator Required for CNS Myelination

2009 ◽  
Vol 138 (1) ◽  
pp. 172-185
Author(s):  
Ben Emery ◽  
Dritan Agalliu ◽  
John D. Cahoy ◽  
Trent A. Watkins ◽  
Jason C. Dugas ◽  
...  
Keyword(s):  
Transcriptional Regulator ◽  
Regulatory Factor ◽  
Gene Regulatory ◽  
Cns Myelination ◽  
Myelin Gene
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