Chromatin Accessibility Dynamics during iPSC Reprogramming
Open accessAbstract
Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC-seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in chromatin states shifting from open to closed (OC) and closed to open (CO), with an initial burst of OC and an ending surge of CO. The OC loci are largely composed of genes associated with a somatic fate, while the CO loci are associated with pluripotency. Factors/conditions known to impede reprogramming prevent OSK-driven OC and skew OC-CO dynamics. While the CO loci are enriched for OSK motifs, the OC loci are not, suggesting alternative mechanisms for chromatin closing. Sap30, a Sin3A corepressor complex component, is required for the OC shift and facilitates reduced H3K27ac deposition at OC loci. These results reveal a chromatin accessibility logic during reprogramming that may apply to other cell-fate decisions.
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Somatic gene loci enriched with somatic state specific TFs from AP-1 and ETS family members are barriers for reprogramming.
“These results are entirely consistent with our earlier findings that somatic gene loci enriched with somatic state specific TFs from AP-1 and ETS family members are barriers for reprogramming10,53,54.”
From The NuRD complex cooperates with SALL4 to orchestrate reprogramming (2023) · cites this paper as [53]
JGES may convert MEFs to iPSCs by closing somatic chromatin and opening pluripotent ones, similar to OSKM and chemical reprogramming.
“JGES may convert MEFs to iPSCs by closing somatic chromatin and opening pluripotent ones, similar to OSKM and chemical reprogramming53,59.”
From The NuRD complex cooperates with SALL4 to orchestrate reprogramming (2023) · cites this paper as [53]
Our earlier work suggests that OSK activates endogenous factors such as Sap30 that will engage Sin3A to close open chromatin in MEFs during early phase of reprogramming.
“Our earlier work suggests that OSK activates endogenous factors such as Sap30 that will engage Sin3A to close open chromatin in MEFs during early phase of reprogramming53.”
From The NuRD complex cooperates with SALL4 to orchestrate reprogramming (2023) · cites this paper as [53]
Cites
Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673 · see citing works
Gene ontology analysis for RNA-seq: accounting for selection bias
Young, M. D., Wakefield, M. J., Smyth, G. K., & Oshlack, A. (2010) · Genome Biology · doi:10.1186/gb-2010-11-2-r14 · Cited by 7,107 · see citing works
GC-Content Normalization for RNA-Seq Data
Risso, D., Schwartz, K., Sherlock, G., & Dudoit, S. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-480 · Cited by 867 · see citing works
A Molecular Roadmap of Reprogramming Somatic Cells into iPS Cells
Polo, J. M., Anderssen, E., Walsh, R. M., Schwarz, B. A., Nefzger, C. M., Lim, S. M., Borkent, M., Apostolou, E., Alaei, S., Cloutier, J., et al. (2012) · Cell · doi:10.1016/j.cell.2012.11.039 · Cited by 861 · see citing works
Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse
Stadtfeld, M., Maherali, N., Breault, D. T., & Hochedlinger, K. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.02.001 · Cited by 823 · see citing works
Pioneer Transcription Factors Target Partial DNA Motifs on Nucleosomes to Initiate Reprogramming
Soufi, A., Garcia, M. F., Jaroszewicz, A., Osman, N., Pellegrini, M., & Zaret, K. S. (2015) · Cell · doi:10.1016/j.cell.2015.03.017 · Cited by 780 · cited 6× · see citing works
“It became apparent that, while all three of OSK can open loci and are thus acting as pioneer TFs to open chromatin (Soufi et al., 2015), S and K could open nearly twice as many loci as O alone, and only 257 O peaks were exclusively opened by O, as many of the O-specific peaks could also be opened by S or K alone (Figu…”
BackgroundInfluentialCooperative 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 · see citing works
EpiFactors: a comprehensive database of human epigenetic factors and complexes
Medvedeva, Y. A., Lennartsson, A., Ehsani, R., Kulakovskiy, I. V., Vorontsov, I. E., Panahandeh, P., Khimulya, G., Kasukawa, T., The FANTOM Consortium, & Drabløs, F. (2015) · Database · doi:10.1093/database/bav067 · Cited by 298 · see citing works
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Chromatin accessibility profiling by ATAC-seq
Grandi, F. C., Modi, H., Kampman, L., & Corces, M. R. (2022) · Nature Protocols · doi:10.1038/s41596-022-00692-9 · Cited by 557 · see citing works
Allele-specific open chromatin in human iPSC neurons elucidates functional disease variants
Zhang, S., Zhang, H., Zhou, Y., Qiao, M., Zhao, S., Kozlova, A., Shi, J., Sanders, A. R., Wang, G., Luo, K., et al. (2020) · Science · doi:10.1126/science.aay3983 · Cited by 127 · see citing works
Li, W., Yang, L., He, Q., Hu, C., Zhu, L., Ma, X., Ma, X., Bao, S., Li, L., Chen, Y., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.06.008 · Cited by 124 · see citing works
Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming
Malik, V., Zimmer, D., & Jauch, R. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2748-5 · Cited by 98 · see citing works
Zhang, T., Huang, K., Zhu, Y., Wang, T., Shan, Y., Long, B., Li, Y., Chen, Q., Wang, P., Zhao, S., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.009757 · Cited by 47 · see citing works
Self-citationThe NuRD complex cooperates with SALL4 to orchestrate reprogramming
Wang, B., Li, C., Ming, J., Wu, L., Fang, S., Huang, Y., Lin, L., Liu, H., Kuang, J., Zhao, C., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38543-0 · Cited by 39 · see citing works
“These results are entirely consistent with our earlier fi ndings that somatic gene loci enriched with somatic state speci fi c TFs from AP-1 and ETS family members are barriersforreprogramming 10,53,54 .”
Self-citation
- Authors
- Li, D., Liu, J., Yang, X., Zhou, C., Guo, J., Wu, C., Qin, Y., Guo, L., He, J., Yu, S., Liu, H., Wang, X., Wu, F., Kuang, J., Hutchins, A. P., Chen, J., & Pei, D.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Hutchins, Andrew P.
- Chen, Jiekai
- Pei, Duanqing
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 21
- Issue
- 6
- Pages
- 819-833.e6
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2775166823
- Cited by
- 251
- References
- 8
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 31 · 2023: 35 · 2022: 35 · 2021: 33 · 2020: 26 · 2019: 29 · 2018: 24 · 2017: 2
- FWCI
- 9.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Key R&D Program of China (2017YFJC040188, 2014CB965200, 2016YFA0101800, 2016YFA0100400)
- National Natural Science Foundation of China (31471242, 31522033, 31550110206, 31421004, 31771424, 31401084, 31501185, 31530038)
- “Frontier Science Research Program” of the CAS (QYZDJ-SSW-SMC009)
- Science and Technology Planning Project of Guangdong Province (2014B050504008, 2014B050502012, 2014B020225002, 2015B020228003)
- Guangdong Natural Science Funds for Distinguished Young Scholars (S2013050014040)
- Youth Innovation Promotion Association of CAS
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- chromatin accessibility, induced pluripotent stem cell reprogramming, Oct4, SOX2, KLF4, cell fate determination, somatic cell reprogramming, H3K27ac, SAP30, mouse embryonic fibroblasts
- MeSH terms
- Kruppel-Like Factor 4, Animals, Cells, Cultured, Chromatin, Octamer Transcription Factor-3, Mice, Kruppel-Like Transcription Factors, SOXB1 Transcription Factors, Induced Pluripotent Stem Cells, Cellular Reprogramming
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