The DOI matches its Crossref record; 85 of the 85 references it cites were found in a registry or an index.
Pioneer Transcription Factors Target Partial DNA Motifs on Nucleosomes to Initiate Reprogramming
Open accessAbstract
SUMMARY Pioneer transcription factors (TFs) access silent chromatin and initiate cell fate changes, using diverse types of DNA binding domains (DBDs). FoxA, the paradigm pioneer TF, has a winged helix DBD that resembles linker histone and thereby binds its target sites on nucleosomes and in compacted chromatin. Herein we compare the nucleosome and chromatin targeting activities of Oct4 (POU DBD), Sox2 (HMG box DBD), Klf4 (zinc finger DBD), and c-Myc (bHLH DBD), which together reprogram somatic cells to pluripotency. Purified Oct4, Sox2, and Klf4 proteins can bind nucleosomes in vitro, and in vivo they preferentially target silent sites enriched for nucleosomes. Pioneer activity relates simply to the ability of a given DBD to target partial motifs displayed on the nucleosome surface. Such partial motif recognition can occur by coordinate binding between factors. Our findings provide insight into how pioneer factors can target naïve chromatin sites.
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“The pioneering model of reprogramming has been proposed for OSKM based on their ability to bind to chromatin not normally accessible by transcription factors60–62.”
From The NuRD complex cooperates with SALL4 to orchestrate reprogramming (2023) · cites this paper as [60]
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“We show here that JGES reprogramming differs markedly from the classic Yamanaka factors OSKM in that JGES relies on Sall4 to engage endogenous NuRD to close open chromatin in MEFs while OSKM relies on pioneering factors to open chromatin in MEFs10,60.”
From The NuRD complex cooperates with SALL4 to orchestrate reprogramming (2023) · cites this paper as [60]
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“The pluripotency factors OCT4, SOX2, and KLF4, when acting as pioneer TFs, bind nucleosomes in vitro by targeting partial and degenerate DNA motifs displayed on the nucleosome surface (64).”
From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [64]
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“which has also been observed at sites of nucleosomal binding by the pioneer and pluripotency factor SOX2 (64).”
From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [64]
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“In contrast with the OSK factors, which function synergistically as pioneer factors during reprogramming, MYC (Fig. 1d) does not exert this function 55 .”
From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [55]
In the citing paper
“For example, a handful pioneer TFs (such as OCT4, SOX2 and KLF4) were shown to bind only partial motifs displayed on the nucleosome surface107.”
From Transcription factors as readers and effectors of DNA methylation (2016) · cites this paper as [107]
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Citations
Cites
Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673 · cited 2×
“The introduction of a defined set of TFs, such as OSKM, into differentiated cells can result in cell-fate conversion (Takahashi and Yamanaka, 2006), and yet it has been clear that the different factors have different contributions or ‘‘strengths’’ in cell-type”
Comparative Protein Modelling by Satisfaction of Spatial Restraints
Šali, A., & Blundell, T. L. (1993) · Journal of Molecular Biology · doi:10.1006/jmbi.1993.1626 · Cited by 12,977
Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R., et al. (2007) · Science · doi:10.1126/science.1151526 · Cited by 10,310 · cited 1×
“, 2012), focusing on the LIN28B locus that is important for reprogramming and pluripotency (Shyh-Chang et al., 2013; Yu et al., 2007).”
The interpretation of protein structures: Estimation of static accessibility
Lee, B., & Richards, F. M. (1971) · Journal of Molecular Biology · doi:10.1016/0022-2836(71)90324-x · Cited by 5,884
FIMO: scanning for occurrences of a given motif
Grant, C. E., Bailey, T. L., & Noble, W. S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr064 · Cited by 4,247
Quantifying similarity between motifs
Gupta, S., Stamatoyannopoulos, J. A., Bailey, T. L., & Noble, W. S. (2007) · Genome Biology · doi:10.1186/gb-2007-8-2-r24 · Cited by 2,058
The SWISS-MODEL Repository and associated resources
Kiefer, F., Arnold, K., Künzli, M., Bordoli, L., & Schwede, T. F. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn750 · Cited by 2,003
MEME-ChIP: motif analysis of large DNA datasets
Machanick, P., & Bailey, T. L. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr189 · Cited by 1,815
Pioneer transcription factors: establishing competence for gene expression
Zaret, K. S., & Carroll, J. S. (2011) · Genes & Development · doi:10.1101/gad.176826.111 · Cited by 1,589 · cited 1×
“However, a select group of transcription factors (TFs) known as pioneer factors have the combined ability to access their target sites in silent chromatin and initiate cell-fate changes (Iwafuchi-Doi and Zaret, 2014; Zaret and Carroll, 2011).”
Self-citationTranscriptional Amplification in Tumor Cells with Elevated c-Myc
Lin, C. Y., Lovén, J., Rahl, P. B., Paranal, R. M., Burge, C. B., Bradner, J. E., Lee, T. I., & Young, R. A. (2012) · Cell · doi:10.1016/j.cell.2012.08.026 · Cited by 1,543 · cited 2×
“However, nucleosome-depleted targets were enriched for a less degenerate E-box motif that we and others have previously reported to be associated with c-Myc binding at enhancers (Lin et al., 2012; Nie et al., 2012; Soufi et al., 2012) (Figure 5B, single arrowhead in bottom panel).”
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The Human Transcription Factors
Lambert, S. A., Jolma, A., Campitelli, L. F., Das, P. K., Yin, Y., Albu, M., Chen, X., Taipale, J., Hughes, T. R., & Weirauch, M. T. (2018) · Cell · doi:10.1016/j.cell.2018.01.029 · Cited by 3,399
Chromatin accessibility and the regulatory epigenome
Klemm, S. L., Shipony, Z., & Greenleaf, W. J. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-018-0089-8 · Cited by 1,793
Stine, Z. E., Walton, Z. E., Altman, B. J., Hsieh, A. L., & Dang, C. V. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0507 · Cited by 1,435
“Indeed, recent work suggests a centrally degenerate E-box motif in closed chromatin may be accessible to MYC using a partially unfolded DNA-binding domain when assisted by other factors, adding a structural rationale to the idea that MYC’s ability to affect gene expression is a confluence of DNA consensus sequence aff…”
BackgroundTranscription factors as readers and effectors of DNA methylation
Zhu, H., Wang, G., & Qian, J. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.83 · Cited by 649
Cooperative Binding of Transcription Factors Orchestrates Reprogramming
Chronis, C., Fiziev, P., Papp, B., Butz, S., Bonora, G., Sabri, S., Ernst, J., & Plath, K. (2017) · Cell · doi:10.1016/j.cell.2016.12.016 · Cited by 555
“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript for human somatic cell reprogramming (Soufi et al., 2012; Soufi et al., 2015) does not act at enhancers in mouse cell reprogramming.”
Metadata
- Authors
- Soufi, A., Garcia, M. F., Jaroszewicz, A., Osman, N., Pellegrini, M., & Zaret, K. S.
- Affiliations
- University of Pennsylvania (US)
- University of California, Los Angeles (US)
- Corresponding author
- Zaret, Kenneth S.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 161
- Issue
- 3
- Pages
- 555-568
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4409934
- OpenAlex
- W1971451591
- Semantic Scholar
- 0a23a104294ce4318a90a1c70248de6cc65b2f1f
- Cited by
- 780
- References
- 85
- Citations by year
- 2026: 54 · 2025: 57 · 2024: 67 · 2023: 78 · 2022: 82 · 2021: 89 · 2020: 77 · 2019: 66 · 2018: 72 · 2017: 59 · 2016: 54 · 2015: 23
- FWCI
- 30.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Human Genome Research Institute (T32HG002536)
- National Institute of General Medical Sciences (P01GM099134)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- pioneer transcription factors, nucleosome binding, DNA-binding domain, chromatin accessibility, cellular reprogramming, pluripotency, Oct4, SOX2, KLF4, c-Myc, HMG box, bHLH, zinc finger, silent chromatin, chromatin remodeling
- MeSH terms
- Kruppel-Like Factor 4, Amino Acid Sequence, DNA, Fibroblasts, Humans, Models, Molecular, Nucleosomes, Transcription Factors, Sequence Alignment, Protein Structure, Tertiary, Octamer Transcription Factor-3, Cell Dedifferentiation, Induced Pluripotent Stem Cells, Nucleotide Motifs, Cellular Reprogramming
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