PMID- 19277982
OWN - NLM
STAT- MEDLINE
DCOM- 20090514
LR  - 20211020
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 220
IP  - 1
DP  - 2009 Jul
TI  - The subnuclear organization of histone gene regulatory proteins and 3' end 
      processing factors of normal somatic and embryonic stem cells is compromised in 
      selected human cancer cell types.
PG  - 129-35
LID - 10.1002/jcp.21740 [doi]
AB  - Human histone gene expression is controlled at the level of transcription 
      initiation and subsequent 3'end processing to generate non-polyadenylated 
      stem-loop containing histone mRNAs. Transcription is controlled at the G1/S phase 
      transition by the Cyclin E/CDK2 mediated induction of p220(NPAT)/HiNF-P complexes 
      at subnuclear domains designated Histone Locus Bodies (HLBs) that associate with 
      histone gene clusters. Histone mRNA maturation is mediated by Lsm10 containing 
      U7snRNP complexes. In normal human somatic and embryonic stem cells, the 6p 
      histone locus, the transcription marker p220(NPAT) and the 3'end processing 
      marker Lsm10 (but not the Cajal Body marker coilin) co-localize, reflecting the 
      assembly of an integrated factory for histone gene expression. Using in situ 
      immuno-fluorescence microscopy and fluorescence in situ hybridization (FISH), we 
      show that this subnuclear organization is compromised in some cancer cell lines. 
      In aneuploid cells, the presence of HLBs correlates with the number of histone 
      gene loci. More importantly, the in situ co-localization of p220(NPAT) and Lsm10 
      is disrupted in HeLa S3 cervical carcinoma cells and MCF7 breast adenocarcinoma 
      cells, with most Lsm10 residing in Cajal Bodies. The finding that the subnuclear 
      integration of transcriptional initiation and 3'end processing of histone gene 
      transcripts is deregulated may be causally linked to tumor-related modifications 
      in molecular pathways controlling histone gene expression during the cell cycle.
FAU - Ghule, Prachi N
AU  - Ghule PN
AD  - Center for Stem Cell Biology and Regenerative Medicine, University of 
      Massachusetts Medical School, Worcester, Massachusetts, USA.
FAU - Dominski, Zbigniew
AU  - Dominski Z
FAU - Lian, Jane B
AU  - Lian JB
FAU - Stein, Janet L
AU  - Stein JL
FAU - van Wijnen, Andre J
AU  - van Wijnen AJ
FAU - Stein, Gary S
AU  - Stein GS
LA  - eng
GR  - R01 GM058921-02/GM/NIGMS NIH HHS/United States
GR  - R37 DE012528/DE/NIDCR NIH HHS/United States
GR  - P01 CA082834-10/CA/NCI NIH HHS/United States
GR  - R01 GM058921/GM/NIGMS NIH HHS/United States
GR  - R01 GM032010-23/GM/NIGMS NIH HHS/United States
GR  - P01 CA082834/CA/NCI NIH HHS/United States
GR  - R01 GM032010/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Histones)
RN  - 0 (LSM10 protein, human)
RN  - 0 (NPAT protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Ribonucleoproteins, Small Nuclear)
SB  - IM
MH  - Aneuploidy
MH  - Cell Cycle
MH  - Cell Cycle Proteins/*genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Embryonic Stem Cells/*metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Histones/*genetics/metabolism
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Intranuclear Space/*metabolism/pathology
MH  - Microscopy, Fluorescence
MH  - Neoplasms/*genetics/metabolism/pathology
MH  - Nuclear Proteins/*genetics/metabolism
MH  - *RNA 3' End Processing
MH  - RNA, Messenger/*metabolism
MH  - Ribonucleoproteins, Small Nuclear/*genetics/metabolism
MH  - Transcription, Genetic
PMC - PMC3167205
MID - NIHMS301281
EDAT- 2009/03/12 09:00
MHDA- 2009/05/15 09:00
PMCR- 2011/09/06
CRDT- 2009/03/12 09:00
PHST- 2009/03/12 09:00 [entrez]
PHST- 2009/03/12 09:00 [pubmed]
PHST- 2009/05/15 09:00 [medline]
PHST- 2011/09/06 00:00 [pmc-release]
AID - 10.1002/jcp.21740 [doi]
PST - ppublish
SO  - J Cell Physiol. 2009 Jul;220(1):129-35. doi: 10.1002/jcp.21740.