ArticleNature chemical biology2021
Permissive epigenomes endow reprogramming competence to transcriptional regulators.
Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- PUS7 pseudouridylation of 7SK orchestrates human somatic cell reprogramming into iPS cells.Nature chemical biology · 2026Article
- Inducing Pluripotency in Somatic Cells: Historical Perspective and Recent Advances.International journal of stem cells · 2024Review
- Exploring the reciprocity between pioneer factors and development.Development (Cambridge, England) · 2024Review
- Review
- DOT1L interaction partner AF10 controls patterning of H3K79 methylation and RNA polymerase II to maintain cell identity.Stem cell reports · 2023Article
- Can we stop one heart from breaking: triumphs and challenges in cardiac reprogramming.Current opinion in genetics & development · 2023Review
- DOT1L is a barrier to histone acetylation during reprogramming to pluripotency.Science advances · 2023Article
- TET (Ten-eleven translocation) family proteins: structure, biological functions and applications.Signal transduction and targeted therapy · 2023Review
- Generation of Induced Pluripotent Stem Cells from Lymphoblastoid Cell Lines by Electroporation of Episomal Vectors.International journal of stem cells · 2023Article
- Review
- BRD9-containing non-canonical BAF complex maintains somatic cell transcriptome and acts as a barrier to human reprogramming.Stem cell reports · 2022Article
- Article
- Article
- p63 silencing induces epigenetic modulation to enhance human cardiac fibroblast to cardiomyocyte-like differentiation.Scientific reports · 2022Article
- Connecting the DOTs on Cell Identity.Frontiers in cell and developmental biology · 2022Review
- Changes in chromatin accessibility landscape and histone H3 core acetylation during valproic acid-induced differentiation of embryonic stem cells.Epigenetics & chromatin · 2021Article
- Key features of the POU transcription factor Oct4 from an evolutionary perspective.Cellular and molecular life sciences : CMLS · 2021Review
- Surf4 facilitates reprogramming by activating the cellular response to endoplasmic reticulum stress.Cell proliferation · 2021Article
- AF10 (MLLT10) prevents somatic cell reprogramming through regulation of DOT1L-mediated H3K79 methylation.Epigenetics & chromatin · 2021Article
- Nicotinamide promotes pancreatic differentiation through the dual inhibition of CK1 and ROCK kinases in human embryonic stem cells.Stem cell research & therapy · 2021Article
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Authors and funding
13 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Identifying molecular and cellular processes that regulate reprogramming competence of transcription factors broadens our understanding of reprogramming mechanisms. In the present study, by a chemical screen targeting major epigenetic pathways in human reprogramming, we discovered that inhibiting specific epigenetic roadblocks including disruptor of telomeric silencing 1-like (DOT1L)-mediated H3K79/K27 methylation, but also other epigenetic pathways, catalyzed by lysine-specific histone demethylase 1A, DNA methyltransferases and histone deacetylases, allows induced pluripotent stem cell generation with almost all OCT factors. We found that simultaneous inhibition of these pathways not only dramatically enhances reprogramming competence of most OCT factors, but in fact enables dismantling of species-dependent reprogramming competence of OCT6, NR5A1, NR5A2, TET1 and GATA3. Harnessing these induced permissive epigenetic states, we performed an additional screen with 98 candidate genes. Thereby, we identified 25 transcriptional regulators (OTX2, SIX3, and so on) that can functionally replace OCT4 in inducing pluripotency. Our findings provide a conceptual framework for understanding how transcription factors elicit reprogramming in dependency of the donor cell epigenome that differs across species.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.