X Chromosome Dosage Influences DNA Methylation Dynamics during Reprogramming to Mouse iPSCs
Summary: A dramatic difference in global DNA methylation between male and female cells characterizes mouse embryonic stem cells (ESCs), unlike somatic cells. We analyzed DNA methylation changes during reprogramming of male and female somatic cells and in resulting induced pluripotent stem cells (iPS...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-05-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671118301462 |
| _version_ | 1818534541073055744 |
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| author | Vincent Pasque Rahul Karnik Constantinos Chronis Paula Petrella Justin Langerman Giancarlo Bonora Juan Song Lotte Vanheer Anupama Sadhu Dimashkie Alexander Meissner Kathrin Plath |
| author_facet | Vincent Pasque Rahul Karnik Constantinos Chronis Paula Petrella Justin Langerman Giancarlo Bonora Juan Song Lotte Vanheer Anupama Sadhu Dimashkie Alexander Meissner Kathrin Plath |
| author_sort | Vincent Pasque |
| collection | DOAJ |
| description | Summary: A dramatic difference in global DNA methylation between male and female cells characterizes mouse embryonic stem cells (ESCs), unlike somatic cells. We analyzed DNA methylation changes during reprogramming of male and female somatic cells and in resulting induced pluripotent stem cells (iPSCs). At an intermediate reprogramming stage, somatic and pluripotency enhancers are targeted for partial methylation and demethylation. Demethylation within pluripotency enhancers often occurs at ESC binding sites of pluripotency transcription factors. Late in reprogramming, global hypomethylation is induced in a female-specific manner. Genome-wide hypomethylation in female cells affects many genomic landmarks, including enhancers and imprint control regions, and accompanies the reactivation of the inactive X chromosome. The loss of one of the two X chromosomes in propagating female iPSCs is associated with genome-wide methylation gain. Collectively, our findings highlight the dynamic regulation of DNA methylation at enhancers during reprogramming and reveal that X chromosome dosage dictates global DNA methylation levels in iPSCs. : Somatic cells can be reprogrammed to iPSCs, inducing reactivation of the inactive X chromosome. Using genome-scale DNA methylation analyses, Plath, Pasque, and colleagues show that iPSCs adopt sex-specific differences in global DNA methylation that correlate with the presence of two active X chromosomes. Upon culture, female iPSCs lose one of the two X chromosomes and adopt male-like DNA methylation. Keywords: induced pluripotency, iPSC, DNA methylation, epigenetics, embryonic stem cells, ESC, pluripotency, reprogramming, X chromosome inactivation |
| first_indexed | 2024-12-11T18:12:59Z |
| format | Article |
| id | doaj.art-d52f7d70ff174c7b822120a3011eba7c |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-11T18:12:59Z |
| publishDate | 2018-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-d52f7d70ff174c7b822120a3011eba7c2022-12-22T00:55:31ZengElsevierStem Cell Reports2213-67112018-05-0110515371550X Chromosome Dosage Influences DNA Methylation Dynamics during Reprogramming to Mouse iPSCsVincent Pasque0Rahul Karnik1Constantinos Chronis2Paula Petrella3Justin Langerman4Giancarlo Bonora5Juan Song6Lotte Vanheer7Anupama Sadhu Dimashkie8Alexander Meissner9Kathrin Plath10Department of Biological Chemistry, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, David Geffen School of Medicine, University of California Los Angeles, 615 Charles E. Young Drive South, BSRB 390D, Los Angeles, CA 90095, USA; KU Leuven – University of Leuven, Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Cancer Institute, Herestraat 49, 3000 Leuven, Belgium; Corresponding authorDepartment of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Broad Institute of MIT and Harvard, Cambridge, MA 02138, USADepartment of Biological Chemistry, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, David Geffen School of Medicine, University of California Los Angeles, 615 Charles E. Young Drive South, BSRB 390D, Los Angeles, CA 90095, USADepartment of Biological Chemistry, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, David Geffen School of Medicine, University of California Los Angeles, 615 Charles E. Young Drive South, BSRB 390D, Los Angeles, CA 90095, USADepartment of Biological Chemistry, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, David Geffen School of Medicine, University of California Los Angeles, 615 Charles E. Young Drive South, BSRB 390D, Los Angeles, CA 90095, USADepartment of Biological Chemistry, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, David Geffen School of Medicine, University of California Los Angeles, 615 Charles E. Young Drive South, BSRB 390D, Los Angeles, CA 90095, USAKU Leuven – University of Leuven, Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Cancer Institute, Herestraat 49, 3000 Leuven, BelgiumKU Leuven – University of Leuven, Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Cancer Institute, Herestraat 49, 3000 Leuven, BelgiumDepartment of Biological Chemistry, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, David Geffen School of Medicine, University of California Los Angeles, 615 Charles E. Young Drive South, BSRB 390D, Los Angeles, CA 90095, USADepartment of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Broad Institute of MIT and Harvard, Cambridge, MA 02138, USADepartment of Biological Chemistry, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, David Geffen School of Medicine, University of California Los Angeles, 615 Charles E. Young Drive South, BSRB 390D, Los Angeles, CA 90095, USA; Corresponding authorSummary: A dramatic difference in global DNA methylation between male and female cells characterizes mouse embryonic stem cells (ESCs), unlike somatic cells. We analyzed DNA methylation changes during reprogramming of male and female somatic cells and in resulting induced pluripotent stem cells (iPSCs). At an intermediate reprogramming stage, somatic and pluripotency enhancers are targeted for partial methylation and demethylation. Demethylation within pluripotency enhancers often occurs at ESC binding sites of pluripotency transcription factors. Late in reprogramming, global hypomethylation is induced in a female-specific manner. Genome-wide hypomethylation in female cells affects many genomic landmarks, including enhancers and imprint control regions, and accompanies the reactivation of the inactive X chromosome. The loss of one of the two X chromosomes in propagating female iPSCs is associated with genome-wide methylation gain. Collectively, our findings highlight the dynamic regulation of DNA methylation at enhancers during reprogramming and reveal that X chromosome dosage dictates global DNA methylation levels in iPSCs. : Somatic cells can be reprogrammed to iPSCs, inducing reactivation of the inactive X chromosome. Using genome-scale DNA methylation analyses, Plath, Pasque, and colleagues show that iPSCs adopt sex-specific differences in global DNA methylation that correlate with the presence of two active X chromosomes. Upon culture, female iPSCs lose one of the two X chromosomes and adopt male-like DNA methylation. Keywords: induced pluripotency, iPSC, DNA methylation, epigenetics, embryonic stem cells, ESC, pluripotency, reprogramming, X chromosome inactivationhttp://www.sciencedirect.com/science/article/pii/S2213671118301462 |
| spellingShingle | Vincent Pasque Rahul Karnik Constantinos Chronis Paula Petrella Justin Langerman Giancarlo Bonora Juan Song Lotte Vanheer Anupama Sadhu Dimashkie Alexander Meissner Kathrin Plath X Chromosome Dosage Influences DNA Methylation Dynamics during Reprogramming to Mouse iPSCs Stem Cell Reports |
| title | X Chromosome Dosage Influences DNA Methylation Dynamics during Reprogramming to Mouse iPSCs |
| title_full | X Chromosome Dosage Influences DNA Methylation Dynamics during Reprogramming to Mouse iPSCs |
| title_fullStr | X Chromosome Dosage Influences DNA Methylation Dynamics during Reprogramming to Mouse iPSCs |
| title_full_unstemmed | X Chromosome Dosage Influences DNA Methylation Dynamics during Reprogramming to Mouse iPSCs |
| title_short | X Chromosome Dosage Influences DNA Methylation Dynamics during Reprogramming to Mouse iPSCs |
| title_sort | x chromosome dosage influences dna methylation dynamics during reprogramming to mouse ipscs |
| url | http://www.sciencedirect.com/science/article/pii/S2213671118301462 |
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