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Cell Rep. 2018 May 15;23(7):1939-1947. doi: 10.1016/j.celrep.2018.04.036.

Reprogramming of Chromatin Accessibility in Somatic Cell Nuclear Transfer Is DNA Replication Independent.

Author information

1
Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
2
Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: yzhang@genetics.med.harvard.edu.

Abstract

Mammalian oocytes have the ability to reset the transcriptional program of differentiated somatic cells into that of totipotent embryos through somatic cell nuclear transfer (SCNT). However, the mechanisms underlying SCNT-mediated reprogramming are largely unknown. To understand the mechanisms governing chromatin reprogramming during SCNT, we profiled DNase I hypersensitive sites (DHSs) in donor cumulus cells and one-cell stage SCNT embryos. To our surprise, the chromatin accessibility landscape of the donor cells is drastically changed to recapitulate that of the in vitro fertilization (IVF)-derived zygotes within 12 hr. Interestingly, this DHS reprogramming takes place even in the presence of a DNA replication inhibitor, suggesting that SCNT-mediated DHS reprogramming is independent of DNA replication. Thus, this study not only reveals the rapid and drastic nature of the changes in chromatin accessibility through SCNT but also establishes a DNA replication-independent model for studying cellular reprogramming.

KEYWORDS:

DNA replication; DNase I hypersensitive sites; SCNT; reprogramming

PMID:
29768195
PMCID:
PMC5988247
DOI:
10.1016/j.celrep.2018.04.036
[Indexed for MEDLINE]
Free PMC Article

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