Facilitators and Impediments of the Pluripotency Reprogramming Factors’ Initial Engagement with the Genome

By A. Soufi, Greg Donahue, K. Zaret. Cell, 2012

868 citations recorded by the source corpus.

SUMMARY The ectopic expression of transcription factors can reprogram cell fate, yet it is unknown how the initial binding of factors to the genome relates functionally to the binding seen in the minority of cells that become reprogrammed. We report a map of Oct4, Sox2, Klf4, and c-Myc (O, S, K, and M) on the human genome during the first 48 hours of reprogramming fibroblasts to pluripotency. Three striking aspects of the initial chromatin binding events include: An unexpected role for c-Myc in facilitating OSK chromatin engagement, the primacy of O, S, and K as pioneer factors at enhancers of genes that promote reprogramming, and megabase-scale chromatin domains spanned by H3K9me3, including many genes required for pluripotency, that prevent initial OSKM binding and impede the efficiency of reprogramming. We find diverse aspects of initial factor binding that must be overcome in the minority of cells that become reprogrammed.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5ad2e2c1f50d033aa430e307342d76ba5ad1172c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

Citations in the corpus

Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo (2015, background): “Furthermore, Pou5f3 and Sox2 are known to be pioneer factors instrumental in reprogramming differentiated cells to a pluripotent state (Soufi et al. 2012, 2015).”
MYC, Metabolism, and Cancer. (2015, background): “Overexpression of MYC can in turn upregulate chromatin modifiers to further alter chromatin accessibility, as suggested by the MYC-mediated induction of the Polycomb complex member EZH2 (40, 57, 58).”
Architectural protein subclasses shape 3D organization of genomes during lineage commitment. (2013, neutral): “Genome-wide analysis of CTCF-independent, ES-specific Smc1 binding sites revealed a strong colocalization with Mediator and pluripotent transcription factors Oct4, Sox2, and Nanog (OSN) (Soufi et al., 2012) (Figure 6A).”
The Sox Family of Transcription Factors: Versatile Regulators of Stem and Progenitor Cell Fate (2013, neutral): “An examination of binding patterns of the four factors 48 hr after their induction in fibroblasts showed that Sox2, Oct4, Klf4, and c-Myc mostly bind to enhancers of early reprogramming genes, which are not yet activated (Soufi et al., 2012).”
H3K4me3 breadth is linked to cell identity and transcriptional consistency (2014, background): “Repressive chromatin marks, such as H3K9me3, are deposited over broad genomic regions ( (cid:1) megabases) (Shah et al., 2013; Souﬁ et al., 2012; Zhu et al., 2013).”
Pioneer Transcription Factors Target Partial DNA Motifs on Nucleosomes to Initiate Reprogramming (2015, neutral): “Other TFs involved in cell reprogramming can target their sites in silent chromatin (Montserrat et al., 2013; Soufi et al., 2012; Takahashi andYamanaka, 2006;Wapinski et al., 2013), but they possess DBDs that differ from that of FoxA.”
Impacts of the ubiquitous factor Zelda on Bicoid-dependent DNA binding and transcription in Drosophila (2014, background): “…the global activators Nanog, Pou5f1, and SoxB1 were recently shown to act as pioneer factors controlling the MZT (Lee et al. 2013; Leichsenring et al. 2013) by establishing active histone marks associated with RNA polymerase II (Pol II) occupancy (Soufi et al. 2012; Leichsenring et al. 2013).”