Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPSC reprogramming
Kai Fu,
Constantinos Chronis,
Abdenour Soufi,
Giancarlo Bonora,
Miguel Edwards,
Stephen T. Smale,
Kenneth S. Zaret,
Kathrin Plath,
Matteo Pellegrini
Affiliations
Kai Fu
Department of Molecular, Cellular and Developmental Biology, Bioinformatics Interdepartmental Program, University of California Los Angeles
Constantinos Chronis
David Geffen School of Medicine, Department of Biological Chemistry, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, Bioinformatics Interdepartmental Program, University of California Los Angeles
Abdenour Soufi
Institute for Regenerative Medicine and Epigenetics Program, Department of Cell and Developmental Biology, Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine
Giancarlo Bonora
Department of Molecular, Cellular and Developmental Biology, Bioinformatics Interdepartmental Program, University of California Los Angeles
Miguel Edwards
Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles
Stephen T. Smale
Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles
Kenneth S. Zaret
Institute for Regenerative Medicine and Epigenetics Program, Department of Cell and Developmental Biology, Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine
Kathrin Plath
David Geffen School of Medicine, Department of Biological Chemistry, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, Bioinformatics Interdepartmental Program, University of California Los Angeles
Matteo Pellegrini
Department of Molecular, Cellular and Developmental Biology, Bioinformatics Interdepartmental Program, University of California Los Angeles
Abstract Background Both human and mouse fibroblasts can be reprogrammed to pluripotency with Oct4, Sox2, Klf4, and c-Myc (OSKM) transcription factors. While both systems generate pluripotency, human reprogramming takes considerably longer than mouse. Results To assess additional similarities and differences, we sought to compare the binding of the reprogramming factors between the two systems. In human fibroblasts, the OSK factors initially target many more closed chromatin sites compared to mouse. Despite this difference, the intra- and intergenic distribution of target sites, target genes, primary binding motifs, and combinatorial binding patterns between the reprogramming factors are largely shared. However, while many OSKM binding events in early mouse cell reprogramming occur in syntenic regions, only a limited number is conserved in human. Conclusions Our findings suggest similar general effects of OSKM binding across these two species, even though the detailed regulatory networks have diverged significantly.
