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Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming
Open accessAbstract
The POU (Pit-Oct-Unc) protein family is an evolutionary ancient group of transcription factors (TFs) that bind specific DNA sequences to direct gene expression programs. The fundamental importance of POU TFs to orchestrate embryonic development and to direct cellular fate decisions is well established, but the molecular basis for this activity is insufficiently understood. POU TFs possess a bipartite 'two-in-one' DNA binding domain consisting of two independently folding structural units connected by a poorly conserved and flexible linker. Therefore, they represent a paradigmatic example to study the molecular basis for the functional versatility of TFs. Their modular architecture endows POU TFs with the capacity to accommodate alternative composite DNA sequences by adopting different quaternary structures. Moreover, associations with partner proteins crucially influence the selection of their DNA binding sites. The plentitude of DNA binding modes confers the ability to POU TFs to regulate distinct genes in the context of different cellular environments. Likewise, different binding modes of POU proteins to DNA could trigger alternative regulatory responses in the context of different genomic locations of the same cell. Prominent POU TFs such as Oct4, Brn2, Oct6 and Brn4 are not only essential regulators of development but have also been successfully employed to reprogram somatic cells to pluripotency and neural lineages. Here we review biochemical, structural, genomic and cellular reprogramming studies to examine how the ability of POU TFs to select regulatory DNA, alone or with partner factors, is tied to their capacity to epigenetically remodel chromatin and drive specific regulatory programs that give cells their identities.
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“We examined the expression patterns of several transcription factor families (Extended Data Fig. 13), including forkhead box (Fox), Krüppel-like factor (Klf), LIM homeobox (Lhx), NKX-homeodomain (Nkx), nuclear receptor (Nr), Paired box (Pax), POU domain (Pou), positive regulatory domain (Prdm), SRY-related HMG-box (Sox), and T-box (Tbx), all of which have been shown to have important roles in”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [102]
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1 retracted
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A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
Yao, Z., van Velthoven, C. T. J., Kunst, M., Zhang, M., McMillen, D., Lee, C., Jung, W., Goldy, J., Abdelhak, A., Aitken, M., et al. (2023) · Nature · doi:10.1038/s41586-023-06812-z · Cited by 1,203
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OCA-T1 and OCA-T2 are coactivators of POU2F3 in the tuft cell lineage
Wu, X., He, X., Ipsaro, J. J., Huang, Y., Preall, J. B., Ng, D., Shue, Y. T., Sage, J., Egeblad, M., Joshua‐Tor, L., et al. (2022) · Nature · doi:10.1038/s41586-022-04842-7 · Cited by 93
Malik, V., Glaser, L. V., Zimmer, D., Velychko, S., Weng, M., Holzner, M., Arend, M., Chen, Y., Srivastava, Y., Veerapandian, V., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11054-7 · Cited by 72
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Metadata
- Authors
- Malik, V., Zimmer, D., & Jauch, R.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Jauch, Ralf
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2018-01-15
- Volume
- 75
- Issue
- 9
- Pages
- 1587-1612
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC11105716
- OpenAlex
- W2783784339
- Cited by
- 98
- References
- 277
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 15 · 2023: 15 · 2022: 11 · 2021: 25 · 2020: 4 · 2019: 10 · 2018: 5
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- Ministry of Science and Technology of the People's Republic of China (2013DFE33080, 2016YFA0100700, 2017YFA0105103)
- National Natural Science Foundation of China (31471238)
- a 100 talent award of the Chinese Academy of Sciences (2014B030301058)
- Science and Technology Planning Projects of Guangdong Province, China (2016A050503038)
- 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
- POU transcription factors, Oct4, Brn2, Oct-6, DNA binding modes, chromatin remodeling, cellular reprogramming, pluripotency, transcription factor-DNA interaction, quaternary structure, epigenetic regulation, embryonic development
- MeSH terms
- Animals, Binding Sites, Cell Differentiation, Chromatin, Humans, Protein Binding, Transcription Factors, POU Domain Factors, Cellular Reprogramming
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