The molecular logic of Nanog-induced self-renewal

Abstract

rue du docteur Roux, Paris 75015. a Equal contributionTranscription factor networks, together with histone modifications and signalling pathways, underlie the establishment and maintenance of gene regulatory architectures associated with the molecular identity of each cell type. However, how master transcription factors individually impact the epigenomic landscape and orchestrate the behaviour of regulatory networks under different environmental constraints is only very partially understood. Here, we show that the transcription factor Nanog deploys multiple distinct mechanisms to enhance embryonic stem cell self-renewal. In the presence of LIF, which fosters self-renewal, Nanog rewires the pluripotency network by promoting chromatin accessibility and binding of other pluripotency factors to thousands of enhancers. In the absence of LIF, Nanog blocks differentiation by sustaining H3K27me3, a repressive histone mark, at developmental regulators. Among those, we show that the repression of Otx2 plays a preponderant role. Our results underscore the versatility of master transcription factors, such as Nanog, to globally influence gene regulation during developmental processes.

Human Medulloblastoma Cell Lines: Investigating on Cancer Stem Cell-Like Phenotype

“…Interestingly, our results on the self-renewal ability of cells through clonal analysis, demonstrated that the capability to form MS is directly correlated to CD133 expression (D283>D341>DAOY), as already reported by other authors [30,46]. This turns out in a significantly higher level of main transcription factors as BMI1, NANOG, and OCT4, all involved in the gene regulatory networks controlling stem cell properties [47][48][49][50]. In agreement with these data, when engrafted in vivo, D283 cells give rise to tumors with high efficiency.…”

MYC and MAX drive the reactivation of the genome after mitosis

“…The genes can be found in Table S2. Statistical associations between selected groups of genes and genomic intervals were assessed with one-sided Fisher's exact tests where increasing distances from the transcription start sites were used to probe the effect of the distance from 100bp to 5Mb, as described 50 . The genome-wide location of Myc/Max motifs (E-boxes) was downloaded from the Jaspar database and only motifs with p<0.001 obtained from the 4 available predictions for slightly different motifs (MA0058.3, MA0059.1, MA0104.4, MA0147.3) were combined and used to compute the number of motifs per ChIP-seq peak.…”