Hartman Institute for Therapeutic Organ Regeneration

Histone variant H3.3 is an essential maternal factor for oocyte reprogramming.

TitleHistone variant H3.3 is an essential maternal factor for oocyte reprogramming.
Publication TypeJournal Article
Year of Publication2014
AuthorsWen D, Banaszynski LA, Liu Y, Geng F, Noh K-M, Xiang J, Elemento O, Rosenwaks Z, C Allis D, Rafii S
JournalProc Natl Acad Sci U S A
Volume111
Issue20
Pagination7325-30
Date Published2014 May 20
ISSN1091-6490
KeywordsAnimals, Cell Nucleus, Cellular Reprogramming, Chromatin, Cytoplasm, Female, Gene Expression Regulation, Developmental, Histones, Mice, Nuclear Transfer Techniques, Oocytes, RNA, Small Interfering, Sequence Analysis, RNA
Abstract

<p>Mature oocyte cytoplasm can reprogram somatic cell nuclei to the pluripotent state through a series of sequential events including protein exchange between the donor nucleus and ooplasm, chromatin remodeling, and pluripotency gene reactivation. Maternal factors that are responsible for this reprogramming process remain largely unidentified. Here, we demonstrate that knockdown of histone variant H3.3 in mouse oocytes results in compromised reprogramming and down-regulation of key pluripotency genes; and this compromised reprogramming for developmental potentials and transcription of pluripotency genes can be rescued by injecting exogenous H3.3 mRNA, but not H3.2 mRNA, into oocytes in somatic cell nuclear transfer embryos. We show that maternal H3.3, and not H3.3 in the donor nucleus, is essential for successful reprogramming of somatic cell nucleus into the pluripotent state. Furthermore, H3.3 is involved in this reprogramming process by remodeling the donor nuclear chromatin through replacement of donor nucleus-derived H3 with de novo synthesized maternal H3.3 protein. Our study shows that H3.3 is a crucial maternal factor for oocyte reprogramming and provides a practical model to directly dissect the oocyte for its reprogramming capacity.</p>

DOI10.1073/pnas.1406389111
Alternate JournalProc Natl Acad Sci U S A
PubMed ID24799717
PubMed Central IDPMC4034224
Grant ListRC2 HL101846 / HL / NHLBI NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States
R01HL097797 / HL / NHLBI NIH HHS / United States
U54CA163167 / CA / NCI NIH HHS / United States
R01 HL097797 / HL / NHLBI NIH HHS / United States
R01 HL119872 / HL / NHLBI NIH HHS / United States
RC2HL101846 / HL / NHLBI NIH HHS / United States
U54 CA163167 / CA / NCI NIH HHS / United States
R01 DK095039 / DK / NIDDK NIH HHS / United States
R01HL119872 / HL / NHLBI NIH HHS / United States
R01DK095039 / DK / NIDDK NIH HHS / United States

Weill Cornell Medicine
Hartman Institute for Therapeutic Organ Regeneration
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