Cited by 98Genomics and Chromatin DynamicsPluripotent Stem Cells ResearchEpigenetics and DNA Methylation

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Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming

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Malik, Vikas, Zimmer, Dennis, Jauch, Ralf·2018·Cellular and Molecular Life Sciences

DOI 10.1007/s00018-018-2748-5PMC PMC11105716

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Abstract

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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Terrell, J. R., & Poon, G. M. K. (2025) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.4c07071
Early epigenetic priming of regeneration studied with a novel transgenic epigenetic reporterPreprint
Khor, J. M., Cisneros, I., Marvel, M., Gore, A. V., Taimatsu, K., Margolin, G., Castranova, D., Goldstein, A. E., Dale, R., & Weinstein, B. M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.21.649771
Additional file 13 of Stop codon readthrough alters the activity of a POU/Oct transcription factor during Drosophila development
Zhao, Y., Lindberg, B. G., Esfahani, S. S., Tang, X., Piazza, S., & Engström, Y. (2021) · Figshare · doi:10.6084/m9.figshare.16569856
Additional file 2 of Stop codon readthrough alters the activity of a POU/Oct transcription factor during Drosophila development
Zhao, Y., Lindberg, B. G., Esfahani, S. S., Tang, X., Piazza, S., & Engström, Y. (2021) · Figshare · doi:10.6084/m9.figshare.16569874
Additional file 17 of Stop codon readthrough alters the activity of a POU/Oct transcription factor during Drosophila development
Zhao, Y., Lindberg, B. G., Esfahani, S. S., Tang, X., Piazza, S., & Engström, Y. (2021) · Figshare · doi:10.6084/m9.figshare.16569868
Additional file 1 of THOC7-AS1/OCT1/FSTL1 axis promotes EMT and serves as a therapeutic target in cutaneous squamous cell carcinoma
Yu, S., Cui, X., Zhou, S., Li, Y., Feng, W., Zhang, X., Zhong, Y., & Zhang, P. (2024) · Figshare · doi:10.6084/m9.figshare.26705304
Additional file 5 of THOC7-AS1/OCT1/FSTL1 axis promotes EMT and serves as a therapeutic target in cutaneous squamous cell carcinoma
Yu, S., Cui, X., Zhou, S., Li, Y., Feng, W., Zhang, X., Zhong, Y., & Zhang, P. (2024) · Figshare · doi:10.6084/m9.figshare.26705316
Additional file 2 of OLMALINC/OCT4/BMP2 axis enhances osteogenic-like phenotype of renal interstitial fibroblasts to participate in Randall’s plaque formation
Zhu, Z., Huang, F., Jiang, Y., Ruan, S., Liu, M., Zhang, Y., Li, Y., Chen, J., Cui, Y., Chen, Z., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22598563
Additional file 11 of Stop codon readthrough alters the activity of a POU/Oct transcription factor during Drosophila development
Zhao, Y., Lindberg, B. G., Esfahani, S. S., Tang, X., Piazza, S., & Engström, Y. (2021) · Figshare · doi:10.6084/m9.figshare.16569850
Additional file 10 of Stop codon readthrough alters the activity of a POU/Oct transcription factor during Drosophila development
Zhao, Y., Lindberg, B. G., Esfahani, S. S., Tang, X., Piazza, S., & Engström, Y. (2021) · Figshare · doi:10.6084/m9.figshare.16569844
Additional file 14 of Stop codon readthrough alters the activity of a POU/Oct transcription factor during Drosophila development
Zhao, Y., Lindberg, B. G., Esfahani, S. S., Tang, X., Piazza, S., & Engström, Y. (2021) · Figshare · doi:10.6084/m9.figshare.16569859
Additional file 4 of THOC7-AS1/OCT1/FSTL1 axis promotes EMT and serves as a therapeutic target in cutaneous squamous cell carcinoma
Yu, S., Cui, X., Zhou, S., Li, Y., Feng, W., Zhang, X., Zhong, Y., & Zhang, P. (2024) · Figshare · doi:10.6084/m9.figshare.26705313
Additional file 3 of Stop codon readthrough alters the activity of a POU/Oct transcription factor during Drosophila development
Zhao, Y., Lindberg, B. G., Esfahani, S. S., Tang, X., Piazza, S., & Engström, Y. (2021) · Figshare · doi:10.6084/m9.figshare.16569877
Additional file 1 of Stop codon readthrough alters the activity of a POU/Oct transcription factor during Drosophila development
Zhao, Y., Lindberg, B. G., Esfahani, S. S., Tang, X., Piazza, S., & Engström, Y. (2021) · Figshare · doi:10.6084/m9.figshare.16569871
Additional file 15 of Stop codon readthrough alters the activity of a POU/Oct transcription factor during Drosophila development
Zhao, Y., Lindberg, B. G., Esfahani, S. S., Tang, X., Piazza, S., & Engström, Y. (2021) · Figshare · doi:10.6084/m9.figshare.16569862
Additional file 3 of OLMALINC/OCT4/BMP2 axis enhances osteogenic-like phenotype of renal interstitial fibroblasts to participate in Randall’s plaque formation
Zhu, Z., Huang, F., Jiang, Y., Ruan, S., Liu, M., Zhang, Y., Li, Y., Chen, J., Cui, Y., Chen, Z., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22598566
Additional file 4 of OLMALINC/OCT4/BMP2 axis enhances osteogenic-like phenotype of renal interstitial fibroblasts to participate in Randall’s plaque formation
Zhu, Z., Huang, F., Jiang, Y., Ruan, S., Liu, M., Zhang, Y., Li, Y., Chen, J., Cui, Y., Chen, Z., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22598569
Additional file 5 of OLMALINC/OCT4/BMP2 axis enhances osteogenic-like phenotype of renal interstitial fibroblasts to participate in Randall’s plaque formation
Zhu, Z., Huang, F., Jiang, Y., Ruan, S., Liu, M., Zhang, Y., Li, Y., Chen, J., Cui, Y., Chen, Z., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22598572
Additional file 3 of THOC7-AS1/OCT1/FSTL1 axis promotes EMT and serves as a therapeutic target in cutaneous squamous cell carcinoma
Yu, S., Cui, X., Zhou, S., Li, Y., Feng, W., Zhang, X., Zhong, Y., & Zhang, P. (2024) · Figshare · doi:10.6084/m9.figshare.26705310
Additional file 16 of Stop codon readthrough alters the activity of a POU/Oct transcription factor during Drosophila development
Zhao, Y., Lindberg, B. G., Esfahani, S. S., Tang, X., Piazza, S., & Engström, Y. (2021) · Figshare · doi:10.6084/m9.figshare.16569865
Additional file 2 of THOC7-AS1/OCT1/FSTL1 axis promotes EMT and serves as a therapeutic target in cutaneous squamous cell carcinoma
Yu, S., Cui, X., Zhou, S., Li, Y., Feng, W., Zhang, X., Zhong, Y., & Zhang, P. (2024) · Figshare · doi:10.6084/m9.figshare.26705307
Additional file 7 of THOC7-AS1/OCT1/FSTL1 axis promotes EMT and serves as a therapeutic target in cutaneous squamous cell carcinoma
Yu, S., Cui, X., Zhou, S., Li, Y., Feng, W., Zhang, X., Zhong, Y., & Zhang, P. (2024) · Figshare · doi:10.6084/m9.figshare.26705322
Additional file 1 of OLMALINC/OCT4/BMP2 axis enhances osteogenic-like phenotype of renal interstitial fibroblasts to participate in Randall’s plaque formation
Zhu, Z., Huang, F., Jiang, Y., Ruan, S., Liu, M., Zhang, Y., Li, Y., Chen, J., Cui, Y., Chen, Z., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22598560
Additional file 8 of Stop codon readthrough alters the activity of a POU/Oct transcription factor during Drosophila development
Zhao, Y., Lindberg, B. G., Esfahani, S. S., Tang, X., Piazza, S., & Engström, Y. (2021) · Figshare · doi:10.6084/m9.figshare.16569892
Additional file 12 of Stop codon readthrough alters the activity of a POU/Oct transcription factor during Drosophila development
Zhao, Y., Lindberg, B. G., Esfahani, S. S., Tang, X., Piazza, S., & Engström, Y. (2021) · Figshare · doi:10.6084/m9.figshare.16569853
Additional file 4 of Stop codon readthrough alters the activity of a POU/Oct transcription factor during Drosophila development
Zhao, Y., Lindberg, B. G., Esfahani, S. S., Tang, X., Piazza, S., & Engström, Y. (2021) · Figshare · doi:10.6084/m9.figshare.16569880
Additional file 6 of THOC7-AS1/OCT1/FSTL1 axis promotes EMT and serves as a therapeutic target in cutaneous squamous cell carcinoma
Yu, S., Cui, X., Zhou, S., Li, Y., Feng, W., Zhang, X., Zhong, Y., & Zhang, P. (2024) · Figshare · doi:10.6084/m9.figshare.26705319
Functional Properties of POU1F1 Mutants in the Transcriptional Regulation of the Thyrotropin β Gene Compared with the Prolactin Gene
Kawauchi, Y., Sasaki, S., Matsushita, A., Nakamura, H. M., Yamashita, M., Kakizawa, K., Ohba, K., Tsuriya, D., Tanaka, T., & Suda, T. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms27010119
Primate lineage specification requires suppression of Alu hypereditingPreprint
Park, E. J., Cui, Y., Levin-Ferreyra, F., Soriano, V. L., Wu, H., Lupión-Garcia, N., Sands, C. M., Pessina, P., Guerra, M. C., Botas, J., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.14.699349
Generation of the induced pluripotent stem cell line ISMMSi061-A from a patient with ataxia, intention tremor, and hypotonia syndrome, childhood-onset
Liu, N. N., Hu, R., Hubbard, S., Salemi, S. E., Baljinnyam, E., Pradhan, P., Smith, G., Webb, B. D., & Marro, S. G. (2026) · Stem Cell Research · doi:10.1016/j.scr.2026.103938
Identification and Functional Characterization of a Novel POU3F4 Frameshift Mutation in a Chinese Family
Fan, S., Guan, Y., Xiang, M., Hongzhe, Y., Zhang, T., Fu, J., Fei, J., Xiao, Y., & Wang, Y. (2026) · Life · doi:10.3390/life16060868
Molecular basis of UV lesion binding and repair inhibition by ETS-family transcription factors
Sivapragasam, S., Terrell, J. R., van der Vaart, A., Germann, M. W., Laughery, M. F., Everly, M. E., Adhikari, S. P., Hrdlicka, P. J., Wyrick, J. J., & Poon, G. M. K. (2026) · Nucleic Acids Research · doi:10.1093/nar/gkag711 · Cited by 1
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Yamada, T., Sepp, M., Sarropoulos, I., & Kaessmann, H. (2026) · Nature Communications · doi:10.1038/s41467-026-75700-7
BRN2 in lineage plasticity: a prostate cancer-focused perspective
Seilani, F., Peng, J., Wu, M., Farahani, M. E., Wang, X., Akinyemi, A. O., & Liu, X. (2026) · Endocrinology · doi:10.1210/endocr/bqag102

Authors: Malik, V., Zimmer, D., & Jauch, R.
Affiliations: Chinese Academy of Sciences (CN)
Corresponding author: Jauch, Ralf
ORCID: Malik, Vikas
Jauch, Ralf
Venue: Cellular and Molecular Life Sciences
Publisher: Springer Science and Business Media LLC
Published: 2018-01-15
Volume: 75
Issue: 9
Pages: 1587-1612
ISSN: 1420-682X (ISSN-L)
1420-9071
DOI: 10.1007/s00018-018-2748-5
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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Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming

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