Dramatic replacement of histone variants during genome remodeling in nuclear-transferred embryos

Buhe Nashun, Tomohiko Akiyama, Masataka G. Suzuki, Fugaku Aoki

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The genome of differentiated somatic nuclei is remodeled to a totipotent state when they are transplanted into enucleated oocytes. To clarify the mechanism of this genome remodeling, we analyzed changes in the composition of core histone variants in nuclear-transferred embryos, since recent evidence has revealed that chromatin structure can be remodeled as a result of variant histone replacement. We found that the donor cell-derived histone H3 variants H3.1, H3.2 and H3.3, as well as H2A and H2A.Z, were rapidly eliminated from the chromatin of nuclei transplanted into enucleated oocytes. Iccompanying this removal, oocyte-stored histone H3 variants and H2A.X were incorporated into the transplanted nuclei, while the incorporation of H2I and H2A.Z was minimal or not detected. The incorporation of these variant histones was DNI replication-independent. These results suggest that most core histone H2A and H3 components are dynamically exchanged between donor nuclei and recipient cytoplasm, which further suggests that replacement of donor cell histones with oocyte-stored histones may play a key role in genome remodeling in nuclear- transferred embryos. In addition, the incorporation patterns of all of the histone variants in the nuclear-transferred embryos were virtually the same as in the fertilized embryos. Only the incorporation pattern of H3.1 differed; it was incorporated into the transplanted donor nuclei, but not in the pronuclei of fertilized embryos. This result suggests that the incorporation of H3.1 has a detrimental effect on the process of genome remodeling and contributes to the low success rate of somatic nuclear cloning.

Original languageEnglish
Pages (from-to)1489-1497
Number of pages9
JournalEpigenetics
Volume6
Issue number12
DOIs
Publication statusPublished - 2011 Jan 1
Externally publishedYes

Fingerprint

Histones
Embryonic Structures
Genome
Oocytes
Chromatin
Organism Cloning
Cytoplasm

Keywords

  • Epigenetics
  • H2A variants
  • H3 variants
  • Nuclear transfer
  • Reprogramming

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Dramatic replacement of histone variants during genome remodeling in nuclear-transferred embryos. / Nashun, Buhe; Akiyama, Tomohiko; Suzuki, Masataka G.; Aoki, Fugaku.

In: Epigenetics, Vol. 6, No. 12, 01.01.2011, p. 1489-1497.

Research output: Contribution to journalArticle

Nashun, Buhe ; Akiyama, Tomohiko ; Suzuki, Masataka G. ; Aoki, Fugaku. / Dramatic replacement of histone variants during genome remodeling in nuclear-transferred embryos. In: Epigenetics. 2011 ; Vol. 6, No. 12. pp. 1489-1497.
@article{1d158a17bb4943c386bf061182733cd2,
title = "Dramatic replacement of histone variants during genome remodeling in nuclear-transferred embryos",
abstract = "The genome of differentiated somatic nuclei is remodeled to a totipotent state when they are transplanted into enucleated oocytes. To clarify the mechanism of this genome remodeling, we analyzed changes in the composition of core histone variants in nuclear-transferred embryos, since recent evidence has revealed that chromatin structure can be remodeled as a result of variant histone replacement. We found that the donor cell-derived histone H3 variants H3.1, H3.2 and H3.3, as well as H2A and H2A.Z, were rapidly eliminated from the chromatin of nuclei transplanted into enucleated oocytes. Iccompanying this removal, oocyte-stored histone H3 variants and H2A.X were incorporated into the transplanted nuclei, while the incorporation of H2I and H2A.Z was minimal or not detected. The incorporation of these variant histones was DNI replication-independent. These results suggest that most core histone H2A and H3 components are dynamically exchanged between donor nuclei and recipient cytoplasm, which further suggests that replacement of donor cell histones with oocyte-stored histones may play a key role in genome remodeling in nuclear- transferred embryos. In addition, the incorporation patterns of all of the histone variants in the nuclear-transferred embryos were virtually the same as in the fertilized embryos. Only the incorporation pattern of H3.1 differed; it was incorporated into the transplanted donor nuclei, but not in the pronuclei of fertilized embryos. This result suggests that the incorporation of H3.1 has a detrimental effect on the process of genome remodeling and contributes to the low success rate of somatic nuclear cloning.",
keywords = "Epigenetics, H2A variants, H3 variants, Nuclear transfer, Reprogramming",
author = "Buhe Nashun and Tomohiko Akiyama and Suzuki, {Masataka G.} and Fugaku Aoki",
year = "2011",
month = "1",
day = "1",
doi = "10.4161/epi.6.12.18206",
language = "English",
volume = "6",
pages = "1489--1497",
journal = "Epigenetics",
issn = "1559-2294",
publisher = "Landes Bioscience",
number = "12",

}

TY - JOUR

T1 - Dramatic replacement of histone variants during genome remodeling in nuclear-transferred embryos

AU - Nashun, Buhe

AU - Akiyama, Tomohiko

AU - Suzuki, Masataka G.

AU - Aoki, Fugaku

PY - 2011/1/1

Y1 - 2011/1/1

N2 - The genome of differentiated somatic nuclei is remodeled to a totipotent state when they are transplanted into enucleated oocytes. To clarify the mechanism of this genome remodeling, we analyzed changes in the composition of core histone variants in nuclear-transferred embryos, since recent evidence has revealed that chromatin structure can be remodeled as a result of variant histone replacement. We found that the donor cell-derived histone H3 variants H3.1, H3.2 and H3.3, as well as H2A and H2A.Z, were rapidly eliminated from the chromatin of nuclei transplanted into enucleated oocytes. Iccompanying this removal, oocyte-stored histone H3 variants and H2A.X were incorporated into the transplanted nuclei, while the incorporation of H2I and H2A.Z was minimal or not detected. The incorporation of these variant histones was DNI replication-independent. These results suggest that most core histone H2A and H3 components are dynamically exchanged between donor nuclei and recipient cytoplasm, which further suggests that replacement of donor cell histones with oocyte-stored histones may play a key role in genome remodeling in nuclear- transferred embryos. In addition, the incorporation patterns of all of the histone variants in the nuclear-transferred embryos were virtually the same as in the fertilized embryos. Only the incorporation pattern of H3.1 differed; it was incorporated into the transplanted donor nuclei, but not in the pronuclei of fertilized embryos. This result suggests that the incorporation of H3.1 has a detrimental effect on the process of genome remodeling and contributes to the low success rate of somatic nuclear cloning.

AB - The genome of differentiated somatic nuclei is remodeled to a totipotent state when they are transplanted into enucleated oocytes. To clarify the mechanism of this genome remodeling, we analyzed changes in the composition of core histone variants in nuclear-transferred embryos, since recent evidence has revealed that chromatin structure can be remodeled as a result of variant histone replacement. We found that the donor cell-derived histone H3 variants H3.1, H3.2 and H3.3, as well as H2A and H2A.Z, were rapidly eliminated from the chromatin of nuclei transplanted into enucleated oocytes. Iccompanying this removal, oocyte-stored histone H3 variants and H2A.X were incorporated into the transplanted nuclei, while the incorporation of H2I and H2A.Z was minimal or not detected. The incorporation of these variant histones was DNI replication-independent. These results suggest that most core histone H2A and H3 components are dynamically exchanged between donor nuclei and recipient cytoplasm, which further suggests that replacement of donor cell histones with oocyte-stored histones may play a key role in genome remodeling in nuclear- transferred embryos. In addition, the incorporation patterns of all of the histone variants in the nuclear-transferred embryos were virtually the same as in the fertilized embryos. Only the incorporation pattern of H3.1 differed; it was incorporated into the transplanted donor nuclei, but not in the pronuclei of fertilized embryos. This result suggests that the incorporation of H3.1 has a detrimental effect on the process of genome remodeling and contributes to the low success rate of somatic nuclear cloning.

KW - Epigenetics

KW - H2A variants

KW - H3 variants

KW - Nuclear transfer

KW - Reprogramming

UR - http://www.scopus.com/inward/record.url?scp=83255193432&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=83255193432&partnerID=8YFLogxK

U2 - 10.4161/epi.6.12.18206

DO - 10.4161/epi.6.12.18206

M3 - Article

C2 - 22139579

AN - SCOPUS:83255193432

VL - 6

SP - 1489

EP - 1497

JO - Epigenetics

JF - Epigenetics

SN - 1559-2294

IS - 12

ER -