PMID- 23903189
OWN - NLM
STAT- MEDLINE
DCOM- 20131030
LR  - 20211021
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 140
IP  - 17
DP  - 2013 Sep
TI  - Histone variant H3.3 maintains a decondensed chromatin state essential for mouse 
      preimplantation development.
PG  - 3624-34
LID - 10.1242/dev.095513 [doi]
AB  - Histone variants can replace canonical histones in the nucleosome and modify 
      chromatin structure and gene expression. The histone variant H3.3 preferentially 
      associates with active chromatin and has been implicated in the regulation of a 
      diverse range of developmental processes. However, the mechanisms by which H3.3 
      may regulate gene activity are unclear and gene duplication has hampered an 
      analysis of H3.3 function in mouse. Here, we report that the specific knockdown 
      of H3.3 in fertilized mouse zygotes leads to developmental arrest at the morula 
      stage. This phenotype can be rescued by exogenous H3.3 but not by canonical H3.1 
      mRNA. Loss of H3.3 leads to over-condensation and mis-segregation of chromosomes 
      as early as the two-cell stage, with corresponding high levels of aneuploidy, but 
      does not appear to affect zygotic gene activation at the two-cell stage or 
      lineage gene transcription at the morula stage. H3.3-deficient embryos have 
      significantly reduced levels of markers of open chromatin, such as H3K36me2 and 
      H4K16Ac. Importantly, a mutation in H3.3K36 that disrupts H3K36 methylation 
      (H3.3K36R) does not rescue the H3.3 knockdown (KD) phenotype. In addition, H3.3 
      KD embryos have increased incorporation of linker H1. Knockdown of Mof (Kat8), an 
      acetyltransferase specific for H4K16, similarly leads to excessive H1 
      incorporation. Remarkably, pan-H1 RNA interference (RNAi) partially rescues the 
      chromosome condensation of H3.3 KD embryos and allows development to the 
      blastocyst stage. These results reveal that H3.3 mediates a balance between open 
      and condensed chromatin that is crucial for the fidelity of chromosome 
      segregation during early mouse development.
FAU - Lin, Chih-Jen
AU  - Lin CJ
AD  - Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, 
      Department of Obstetrics and Gynecology and Center for Reproductive Sciences, 
      University of California San Francisco, 35 Medical Center Way, San Francisco, CA 
      94143, USA.
FAU - Conti, Marco
AU  - Conti M
FAU - Ramalho-Santos, Miguel
AU  - Ramalho-Santos M
LA  - eng
GR  - P30 DK063720/DK/NIDDK NIH HHS/United States
GR  - 1U54HD055764/HD/NICHD NIH HHS/United States
GR  - U54 HD055764/HD/NICHD NIH HHS/United States
GR  - DP2 OD004698/OD/NIH HHS/United States
GR  - DP2OD004698/OD/NIH HHS/United States
GR  - P50 HD055764/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130731
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Chromatin)
RN  - 0 (Histones)
RN  - 0 (Morpholinos)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (Kat8 protein, mouse)
SB  - IM
MH  - Animals
MH  - Chromatin/*metabolism
MH  - Chromosome Segregation/genetics/*physiology
MH  - Cytogenetic Analysis
MH  - Embryonic Development/genetics/*physiology
MH  - Gene Expression Regulation, Developmental/*physiology
MH  - Gene Knockdown Techniques
MH  - Histone Acetyltransferases/genetics
MH  - Histones/genetics/*metabolism
MH  - Mice
MH  - Microscopy, Confocal
MH  - Microscopy, Fluorescence
MH  - Morpholinos/genetics
MH  - RNA, Small Interfering/genetics
MH  - Real-Time Polymerase Chain Reaction
PMC - PMC3742145
OTO - NOTNLM
OT  - Chromatin condensation
OT  - Chromosome segregation
OT  - Epigenetics
OT  - Histone acetylation
OT  - Histone methylation
OT  - Histone variant H3.3
OT  - Linker histone H1
OT  - Mouse preimplantation development
EDAT- 2013/08/02 06:00
MHDA- 2013/10/31 06:00
PMCR- 2014/09/01
CRDT- 2013/08/02 06:00
PHST- 2013/08/02 06:00 [entrez]
PHST- 2013/08/02 06:00 [pubmed]
PHST- 2013/10/31 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - dev.095513 [pii]
AID - 10.1242/dev.095513 [doi]
PST - ppublish
SO  - Development. 2013 Sep;140(17):3624-34. doi: 10.1242/dev.095513. Epub 2013 Jul 31.