The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Mbd3/NURD Complex Regulates Expression of 5-Hydroxymethylcytosine Marked Genes in Embryonic Stem Cells
Open accessAbstract
SUMMARY Numerous chromatin regulators are required for embryonic stem (ES) cell self-renewal and pluripotency, but few have been studied in detail. Here, we examine the roles of several chromatin regulators whose loss affects the pluripotent state of ES cells. We find that Mbd3 and Brg1 antagonistically regulate a common set of genes by regulating promoter nucleosome occupancy. Furthermore, both Mbd3 and Brg1 play key roles in the biology of 5-hydroxymethylcytosine (5hmC): Mbd3 co-localizes with Tet1 and 5hmC in vivo, Mbd3 knockdown preferentially affects expression of 5hmC-marked genes, Mbd3 localization is Tet1-dependent, and Mbd3 preferentially binds to 5hmC relative to 5-methylcytosine in vitro. Finally, both Mbd3 and Brg1 are themselves required for normal levels of 5hmC in vivo. Together, our results identify an effector for 5hmC, and reveal that control of gene expression by antagonistic chromatin regulators is a surprisingly common regulatory strategy in ES cells.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Smyth, G. K. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1027 · Cited by 11,829
DAVID: Database for Annotation, Visualization, and Integrated Discovery
Dennis, G., Sherman, B. T., Hosack, D. A., Yang, J., Gao, W., Lane, H. C., & Lempicki, R. A. (2003) · Genome Biology · doi:10.1186/gb-2003-4-5-p3 · Cited by 9,327
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.041 · Cited by 5,361
The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain
Kriaucionis, S., & Heintz, N. (2009) · Science · doi:10.1126/science.1169786 · Cited by 2,700
Zhang, Y., Ng, H.-H., Erdjument-Bromage, H., Tempst, P., Bird, A., & Reinberg, D. (1999) · Genes & Development · doi:10.1101/gad.13.15.1924 · Cited by 1,103
Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells
Wu, H., D’Alessio, A. C., Ito, S., Xia, K., Wang, Z., Cui, K., Zhao, K., Eve Sun, Y., & Zhang, Y. (2011) · Nature · doi:10.1038/nature09934 · Cited by 646
An Oct4-Centered Protein Interaction Network in Embryonic Stem Cells
van den Berg, D. L. C., Snoek, T., Mullin, N. P., Yates, A., Bezstarosti, K., Demmers, J., Chambers, I., & Poot, R. A. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.02.014 · Cited by 542
Dawlaty, M. M., Ganz, K., Powell, B. E., Hu, Y.-C., Markoulaki, S., Cheng, A. W., Gao, Q., Kim, J., Choi, S.-W., Page, D. C., et al. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.07.010 · Cited by 508
Functional analysis of mouse Polycomb group genes.
van Lohuizen, M. (1998) · Cellular and Molecular Life Sciences (CMLS) · doi:10.1007/s000180050126 · Cited by 79
Cited by
DNA methylation: roles in mammalian development
Smith, Z. D., & Meissner, A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3354 · Cited by 3,045
Modification of Enhancer Chromatin: What, How, and Why?
Calo, E., & Wysocka, J. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.01.038 · Cited by 1,457
Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials
Cheng, Y., He, C., Wang, M., Ma, X., Mo, F., Yang, S., Han, J., & Wei, X. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0095-0 · Cited by 1,097
“These drugs are usually small molecular inhibitors and directly target catalytic sites rather than incorporating into DNA.”
BackgroundInfluentialReversing DNA Methylation: Mechanisms, Genomics, and Biological Functions
Wu, H., & Zhang, Y. (2014) · Cell · doi:10.1016/j.cell.2013.12.019 · Cited by 1,065
“The transcriptional activation role of TET1may be dependent on its 5mC oxidation activity to maintain unmethylated states at active promoters or distal enhancers (Ficz et al., 2011; Shen et al., 2013; Wu et al., 2011b); in contrast, a role of TET1 in transcriptional repression may be related to its physical interactio…”
InfluentialDynamic Readers for 5-(Hydroxy)Methylcytosine and Its Oxidized Derivatives
Spruijt, C. G., Gnerlich, F., Smits, A. H., Pfaffeneder, T., Jansen, P. W. T. C., Bauer, C., Münzel, M., Wagner, M., Müller, M., Khan, F., et al. (2013) · Cell · doi:10.1016/j.cell.2013.02.004 · Cited by 973
MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system
Mellén, M., Ayata, P., Dewell, S., Kriaucionis, S., & Heintz, N. (2012) · Cell · doi:10.1016/j.cell.2012.11.022 · Cited by 943
TETonic shift: biological roles of TET proteins in DNA demethylation and transcription
Pastor, W. A., Aravind, L., & Rao, A. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3589 · Cited by 897
Chromatin modifiers and remodellers: regulators of cellular differentiation
Chen, T., & Dent, S. Y. R. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3607 · Cited by 619
The role of mutations in epigenetic regulators in myeloid malignancies
Shih, A. H., Abdel-Wahab, O., Patel, J. P., & Levine, R. L. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3343 · Cited by 611
Methyl-cpG-binding domain proteins: readers of the epigenome
Du, Q., Luu, P.-L., Stirzaker, C., & Clark, S. J. (2015) · Epigenomics · doi:10.2217/epi.15.39 · Cited by 544
Tet-Mediated Formation of 5-Hydroxymethylcytosine in RNA
Fu, L., Guerrero, C. R., Zhong, N., Amato, N. J., Liu, Y., Liu, S., Cai, Q., Ji, D., Jin, S.-G., Niedernhofer, L. J., et al. (2014) · Journal of the American Chemical Society · doi:10.1021/ja505305z · Cited by 404
Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin
Masuda, T., Wang, X., Maeda, M., Canver, M. C., Sher, F., Funnell, A. P. W., Fisher, C., Suciu, M., Martyn, G. E., Norton, L. J., et al. (2016) · Science · doi:10.1126/science.aad3312 · Cited by 373
Methylation-Dependent and -Independent Genomic Targeting Principles of the MBD Protein Family
Baubec, T., Ivánek, R., Lienert, F., & Schübeler, D. (2013) · Cell · doi:10.1016/j.cell.2013.03.011 · Cited by 365
Neri, F., Incarnato, D., Krepelova, A., Rapelli, S., Pagnani, A., Zecchina, R., Parlato, C., & Oliviero, S. (2013) · Genome Biology · doi:10.1186/gb-2013-14-8-r91 · Cited by 179
Potential functional roles of DNA demethylation intermediates
Song, C.-X., & He, C. (2013) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2013.07.003 · Cited by 154
Tet Enzymes, Variants, and Differential Effects on Function
Melamed, P., Yosefzon, Y., David, C., Tsukerman, A., & Pnueli, L. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00022 · Cited by 130
Role of LDB1 in the transition from chromatin looping to transcription activation
Krivega, I., Dale, R. K., & Dean, A. (2014) · Genes & Development · doi:10.1101/gad.239749.114 · Cited by 125
Evolving insights on how cytosine methylation affects protein-DNA binding
Dantas Machado, A. C., Zhou, T., Rao, S., Goel, P., Rastogi, C., Lazarovici, A., Bussemaker, H. J., & Rohs, R. (2015) · Briefings in Functional Genomics · doi:10.1093/bfgp/elu040 · Cited by 124
NuRD Blocks Reprogramming of Mouse Somatic Cells into Pluripotent Stem Cells
Luo, M., Ling, T., Xie, W., Sun, H., Zhou, Y., Zhu, Q., Shen, M., Zong, L., Lyu, G., Zhao, Y., et al. (2013) · Stem Cells · doi:10.1002/stem.1374 · Cited by 104
Epigenetic reprogramming of melanoma cells by vitamin C treatment
Gustafson, C. B., Yang, C., Dickson, K. M., Shao, H., Van Booven, D., Harbour, J. W., Liu, Z.-J., & Wang, G. (2015) · Clinical Epigenetics · doi:10.1186/s13148-015-0087-z · Cited by 90
Kallin, E. M., Rodríguez-Ubreva, J., Christensen, J., Cimmino, L., Aifantis, I., Helin, K., Ballestar, E., & Graf, T. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.08.007 · Cited by 92
“Third, OH-MeC might serve as a docking site itself to recruit additional transcription regulators (Yildirim et al., 2011).”
BackgroundDigging deep into “dirty” drugs – modulation of the methylation machinery
Pleyer, L., & Greil, R. (2015) · Drug Metabolism Reviews · doi:10.3109/03602532.2014.995379 · Cited by 84
“…marks in succeeding DNA-replication cycles (Pastor et al., 2011; Valinluck et al., 2004); (iii) 5-hmC blocks the binding of MBPs, in particular MeCP2 or MBD3, which usually confer transcriptional silencing (Ko et al., 2010; Pastor et al., 2011; Valinluck et al., 2004; Yildirim et al., 2011).”
Background5-hydroxymethylcytosine is highly dynamic across human fetal brain development
Spiers, H., Hannon, E., Schalkwyk, L. C., Bray, N. J., & Mill, J. (2017) · BMC Genomics · doi:10.1186/s12864-017-4091-x · Cited by 80
Mor, N., Rais, Y., Sheban, D., Peles, S., Aguilera-Castrejon, A., Zviran, A., Elinger, D., Viukov, S., Geula, S., Krupalnik, V., et al. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.07.004 · Cited by 79
Bode, D., Yu, L., Tate, P., Pardo, M., & Choudhary, J. (2016) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m115.053207 · Cited by 50
Colquitt, B. M., Markenscoff-Papadimitriou, E., Duffié, R., & Lomvardas, S. (2014) · Neuron · doi:10.1016/j.neuron.2014.07.013 · Cited by 38
Hainer, S. J., & Fazzio, T. G. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.08.071 · Cited by 33
Self-citationGuan, W., Guyot, R., Samarut, J., Flamant, F., Wong, J., & Gauthier, K. C. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1702192114 · Cited by 32
Liu, Y., He, T., Li, Z., Sun, Z., Wang, S., Shen, H., Hou, L., Li, S., Wei, Y., Zhuo, B., et al. (2023) · iScience · doi:10.1016/j.isci.2023.108312 · Cited by 15
TET dioxygenases localize at splicing speckles and promote RNA splicing
Hastert, F. D., Weber, J., Bauer, C., Zhadan, A., Singh, D. N. D., Dix, T. C., Arnold, R., Bessonov, S., Soller, M., Leonhardt, H., et al. (2025) · Nucleus · doi:10.1080/19491034.2025.2536902 · Cited by 5
“In the past, the link between TET1 and the NuRD chromatin remodeling complex was reported [110], which mediates gene repression to maintain the pluripotent state of ESCs.”
TET dioxygenases localize at splicing speckles and promote RNA splicing
Hastert, F. D., Weber, J., Bauer, C., Zhadan, A., Singh, D. N. D., Dix, T. C., Arnold, R., Bessonov, S., Soller, M., Leonhardt, H., et al. (2025) · doi:10.1101/2025.03.07.641893
Metadata
- Authors
- Yildirim, O., Li, R., Hung, J.-H., Chen, P. B., Dong, X., Ee, L.-S., Weng, Z., Rando, O. J., & Fazzio, T. G.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 147
- Issue
- 7
- Pages
- 1498-1510
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2010984732
- Cited by
- 450
- References
- 9
- FWCI
- 21.16
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
