Document Detail


Staged assembly of histone gene expression machinery at subnuclear foci in the abbreviated cell cycle of human embryonic stem cells.
MedLine Citation:
PMID:  18957539     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human embryonic stem (hES) cells have an abbreviated G(1) phase of the cell cycle. How cells expedite G(1) events that are required for the initiation of S phase has not been resolved. One key regulatory pathway that controls G(1)/S-phase transition is the cyclin E/CDK2-dependent activation of the coactivator protein nuclear protein, ataxia-telangiectasia locus/histone nuclear factor-P (p220(NPAT)/HiNF-P) complex that induces histone gene transcription. In this study, we use the subnuclear organization of factors controlling histone gene expression to define mechanistic differences in the G(1) phase of hES and somatic cells using in situ immunofluorescence microscopy and fluorescence in situ hybridization (FISH). We show that histone gene expression is supported by the staged assembly and modification of a unique subnuclear structure that coordinates initiation and processing of transcripts originating from histone gene loci. Our results demonstrate that regulatory complexes that mediate transcriptional initiation (e.g., p220(NPAT)) and 3'-end processing (e.g., Lsm10, Lsm11, and SLBP) of histone gene transcripts colocalize at histone gene loci in dedicated subnuclear foci (histone locus bodies) that are distinct from Cajal bodies. Although appearance of CDK2-phosphorylated p220(NPAT) in these domains occurs at the time of S-phase entry, histone locus bodies are formed approximately 1 to 2 h before S phase in embryonic cells but 6 h before S phase in somatic cells. These temporal differences in the formation of histone locus bodies suggest that the G(1) phase of the cell cycle in hES cells is abbreviated in part by contraction of late G(1).
Authors:
Prachi N Ghule; Zbigniew Dominski; Xiao-Cui Yang; William F Marzluff; Klaus A Becker; J Wade Harper; Jane B Lian; Janet L Stein; Andre J van Wijnen; Gary S Stein
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-10-28
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  105     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-05     Completed Date:  2008-12-22     Revised Date:  2014-09-16    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16964-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle / genetics*
Cell Cycle Proteins / metabolism
Embryonic Stem Cells / cytology,  metabolism*
Histones / genetics*,  metabolism
Humans
In Situ Hybridization, Fluorescence
Intranuclear Space / metabolism*
Mice
Microscopy, Fluorescence
Nuclear Proteins / metabolism
RNA-Binding Proteins / metabolism
Ribonucleoproteins, Small Nuclear / metabolism
mRNA Cleavage and Polyadenylation Factors / metabolism
Grant Support
ID/Acronym/Agency:
R01 GM032010/GM/NIGMS NIH HHS; R01 GM032010/GM/NIGMS NIH HHS; R01 GM054137/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Histones; 0/LSM10 protein, human; 0/Lsm11 protein, human; 0/NPAT protein, human; 0/Nuclear Proteins; 0/RNA-Binding Proteins; 0/Ribonucleoproteins, Small Nuclear; 0/SLBP protein, human; 0/mRNA Cleavage and Polyadenylation Factors
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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