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High Resolution Methylome Analysis Reveals Widespread Functional Hypomethylation during Adult Human Erythropoiesis
Abstract
Differentiation of hematopoietic stem cells to red cells requires coordinated expression of numerous erythroid genes and is characterized by nuclear condensation and extrusion during terminal development. To understand the regulatory mechanisms governing these widespread phenotypic changes, we conducted a high resolution methylomic and transcriptomic analysis of six major stages of human erythroid differentiation. We observed widespread epigenetic differences between early and late stages of erythropoiesis with progressive loss of methylation being the dominant change during differentiation. Gene bodies, intergenic regions, and CpG shores were preferentially demethylated during erythropoiesis. Epigenetic changes at transcription factor binding sites correlated significantly with changes in gene expression and were enriched for binding motifs for SCL, MYB, GATA, and other factors not previously implicated in erythropoiesis. Demethylation at gene promoters was associated with increased expression of genes, whereas epigenetic changes at gene bodies correlated inversely with gene expression. Important gene networks encoding erythrocyte membrane proteins, surface receptors, and heme synthesis proteins were found to be regulated by DNA methylation. Furthermore, integrative analysis enabled us to identify novel, potential regulatory areas of the genome as evident by epigenetic changes in a predicted PU.1 binding site in intron 1 of the GATA1 gene. This intronic site was found to be conserved across species and was validated to be a novel PU.1 binding site by quantitative ChIP in erythroid cells. Altogether, our study provides a comprehensive analysis of methylomic and transcriptomic changes during erythroid differentiation and demonstrates that human terminal erythropoiesis is surprisingly associated with hypomethylation of the genome.
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“PU.1 expression was high in human CD34+ cells and diminished in differentiated CD36+ cells (47) (Fig. 1F).”
From Histone deacetylase 1 activates PU.1 gene transcription through regulating TAF9 deacetylation and transcription factor IID assembly (2017) · cites this paper as [47]
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Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382
Irizarry, R. A., Ladd-Acosta, C., Wen, B., Wu, Z., Montano, C., Onyango, P., Cui, H., Gabo, K., Rongione, M., Webster, M., et al. (2009) · Nature Genetics · doi:10.1038/ng.298 · Cited by 2,177
Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells
Ball, M. P., Li, J. B., Gao, Y., Lee, J., LeProust, E. M., Park, I., Xie, B., Daley, G. Q., & Church, G. M. (2009) · Nature Biotechnology · doi:10.1038/nbt.1533 · Cited by 1,122
DNA Methylation Signatures Identify Biologically Distinct Subtypes in Acute Myeloid Leukemia
Figueroa, M. E., Lugthart, S., Li, Y., Erpelinck-Verschueren, C., Deng, X., Christos, P. J., Schifano, E., Booth, J., van Putten, W., Skrabanek, L., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.11.020 · Cited by 833
Self-citationComprehensive methylome map of lineage commitment from haematopoietic progenitors
Ji, H., Ehrlich, L. I. R., Seita, J., Murakami, P. N., Doi, A., Lindau, P., Lee, H.-J., Aryee, M. J., Irizarry, R. A., Kim, K., et al. (2010) · Nature · doi:10.1038/nature09367 · Cited by 657
Comparative isoschizomer profiling of cytosine methylation: The HELP assay
Khulan, B., Thompson, R. F., Ye, K., Fazzari, M. J., Suzuki, M., Stasiek, E., Figueroa, M. E., Glass, J. L., Chen, Q., Montagna, C., et al. (2006) · Genome Research · doi:10.1101/gr.5273806 · Cited by 396
Self-citationTrowbridge, J. J., Snow, J. W., Kim, J., & Orkin, S. H. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2009.08.016 · Cited by 373
Global DNA Demethylation During Mouse Erythropoiesis in Vivo
Shearstone, J. R., Pop, R., Bock, C., Boyle, P., Meissner, A., & Socolovsky, M. (2011) · Science · doi:10.1126/science.1207306 · Cited by 161
Oda, M., Glass, J. L., Thompson, R. F., Mo, Y., Olivier, E. N., Figueroa, M. E., Selzer, R. R., Richmond, T., Zhang, X., Dannenberg, L. O., et al. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp260 · Cited by 157
Self-citationStopka, T., Amanatullah, D. F., Papetti, M., & Skoultchi, A. I. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600834 · Cited by 154
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Self-citationAlvarez, H., Opalinska, J., Zhou, L., Sohal, D. P. S., Fazzari, M. J., Yu, Y., Montagna, C., Montgomery, E. A., Canto, M. I., Dunbar, K. B., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001356 · Cited by 142
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Esteller, M. (2003) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-0081-0_5 · Cited by 137
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Baldewijns, M. M. L. L., van Vlodrop, I. J. H., Schouten, L. J., Soetekouw, P. M. M. B., de Bruïne, A. P., & van Engeland, M. (2008) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2007.12.002 · Cited by 134
Site-specific DNA methylation by a complex of PU.1 and Dnmt3a/b
Suzuki, M., Yamada, T., Kihara-Negishi, F., Sakurai, T., Hara, E., Tenen, D. G., Hozumi, N., & Oikawa, T. (2006) · Oncogene · doi:10.1038/sj.onc.1209272 · Cited by 132
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Rekhtman, N., Choe, K. S., Matushansky, I., Murray, S., Stopka, T., & Skoultchi, A. I. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.21.7460-7474.2003 · Cited by 102
Self-citationFigueroa, M. E., Wouters, B. J., Skrabanek, L. A., Glass, J. L., Li, Y., Erpelinck-Verschueren, C. A. J., Langerak, A. W., Löwenberg, B., Fazzari, M. J., Greally, J. M., et al. (2009) · Blood · doi:10.1182/blood-2008-08-172387 · Cited by 90
Self-citationAn Integrative Genomic and Epigenomic Approach for the Study of Transcriptional Regulation
Figueroa, M. E., Reimers, M., Thompson, R. F., Ye, K. Q., Li, Y., Selzer, R. R., Fridriksson, J., Paietta, E. M., Wiernik, P. H., Green, R. D., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001882 · Cited by 88
Self-citationGenetic and epigenetic alterations during renal carcinogenesis.
Arai, E., & Kanai, Y. (2010) · PubMed · Cited by 80
Wontakal, S. N., Guo, X., Smith, C., MacCarthy, T., Bresnick, E. H., Bergman, A., Snyder, M. P., Weissman, S. M., Zheng, D., & Skoultchi, A. I. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1121019109 · Cited by 79
Self-citationErythroid and megakaryocytic transformation
Wickrema, A., & Crispino, J. D. (2007) · Oncogene · doi:10.1038/sj.onc.1210763 · Cited by 63
Self-citationAlternative pre-mRNA splicing switches modulate gene expression in late erythropoiesis
Yamamoto, M. L., Clark, T. A., Gee, S. L., Kang, J.-A., Schweitzer, A. C., Wickrema, A., & Conboy, J. G. (2009) · Blood · doi:10.1182/blood-2008-05-160325 · Cited by 61
Self-citationAn analytical pipeline for genomic representations used for cytosine methylation studies
Thompson, R. F., Reimers, M., Khulan, B., Gissot, M., Richmond, T., Chen, Q., Zheng, X., Kim, K., & Greally, J. M. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn096 · Cited by 55
Self-citationWontakal, S. N., Guo, X., Will, B., Shi, M., Raha, D., Mahajan, M. C., Weissman, S., Snyder, M., Steidl, U., Zheng, D., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001392 · Cited by 53
Self-citationKang, J.-W., Zhou, Y., Weis, T. L., Liu, H., Ulaszek, J., Satgurunathan, N., Zhou, L., van Besien, K., Crispino, J. D., Verma, A., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m706712200 · Cited by 48
Self-citationIntron 1 Elements Promote Erythroid-specific GATA-1 Gene Expression
Seshasayee, D., Geiger, J. N., Gaines, P. C. W., & Wojchowski, D. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002931200 · Cited by 23
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Metadata
- Authors
- Yu, Y., Mo, Y., Ebenezer, D., Bhattacharyya, S., Liu, H., Sundaravel, S., Giricz, O., Wontakal, S., Cartier, J., Caces, B., Artz, A., Nischal, S., Bhagat, T., Bathon, K., Maqbool, S., Gligich, O., Suzuki, M., Steidl, U., Godley, L., Skoultchi, A., Greally, J., Wickrema, A., & Verma, A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 288
- Issue
- 13
- Pages
- 8805-8814
- ISSN
- 0021-9258
- Cited by
- 43
- References
- 26
- Language
- en
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- creativecommons.org/licenses/by/4.0/ (vor, 2770 d)
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