PMID- 12833066
OWN - NLM
STAT- MEDLINE
DCOM- 20030814
LR  - 20171116
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 5
IP  - 7
DP  - 2003 Jul
TI  - Heritable gene silencing in lymphocytes delays chromatid resolution without 
      affecting the timing of DNA replication.
PG  - 668-74
AB  - Temporal control of DNA replication has been implicated in epigenetic regulation 
      of gene expression on the basis of observations that certain tissue-specific 
      genes replicate earlier in expressing than non-expressing cells. Here, we show 
      evidence that several leukocyte-specific genes replicate early in lymphocytes 
      regardless of their transcription and also in fibroblasts, where these genes are 
      never normally expressed. Instead, the heritable silencing of some genes (Rag-1, 
      TdT, CD8alpha and lambda5) and their spatial recruitment to heterochromatin 
      domains within the nucleus of lymphocytes resulted in a markedly delayed 
      resolution of sister chromatids into doublet signals discernable by 3D 
      fluorescence in situ hybridization (FISH). Integration of transgenes within 
      heterochromatin (in cis) did, however, confer late replication and this was 
      reversed after variegated transgene expression. These findings emphasise that 
      chromosomal location is important for defining the replication timing of genes 
      and show that retarded sister-chromatid resolution is a novel feature of inactive 
      chromatin.
FAU - Azuara, Veronique
AU  - Azuara V
AD  - Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College 
      School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. 
      v.azuara@csc.mrc.ac.uk
FAU - Brown, Karen E
AU  - Brown KE
FAU - Williams, Ruth R E
AU  - Williams RR
FAU - Webb, Natasha
AU  - Webb N
FAU - Dillon, Niall
AU  - Dillon N
FAU - Festenstein, Richard
AU  - Festenstein R
FAU - Buckle, Veronica
AU  - Buckle V
FAU - Merkenschlager, Matthias
AU  - Merkenschlager M
FAU - Fisher, Amanda G
AU  - Fisher AG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (CD8 Antigens)
RN  - 0 (CD8alpha antigen)
RN  - 0 (Cerebrospinal Fluid Proteins)
RN  - 0 (Heterochromatin)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (gamma 5 protein, human)
RN  - 128559-51-3 (RAG-1 protein)
RN  - EC 2.7.7.31 (DNA Nucleotidylexotransferase)
SB  - IM
MH  - Animals
MH  - CD8 Antigens/genetics/metabolism
MH  - Cell Cycle/*genetics
MH  - Cell Line
MH  - Cell Nucleus/genetics/metabolism
MH  - Cerebrospinal Fluid Proteins/genetics/metabolism
MH  - Chromatids/*genetics
MH  - DNA Nucleotidylexotransferase/genetics/metabolism
MH  - DNA Replication/*genetics
MH  - Fibroblasts/cytology/*metabolism
MH  - Flow Cytometry
MH  - Gene Expression Regulation/*genetics
MH  - Gene Silencing/*physiology
MH  - Heterochromatin/genetics
MH  - Homeodomain Proteins/genetics/metabolism
MH  - Humans
MH  - Lymphocytes/cytology/*metabolism
MH  - Mice
MH  - Transgenes/genetics
EDAT- 2003/07/02 05:00
MHDA- 2003/08/15 05:00
CRDT- 2003/07/02 05:00
PHST- 2003/02/25 00:00 [received]
PHST- 2003/04/30 00:00 [accepted]
PHST- 2003/07/02 05:00 [pubmed]
PHST- 2003/08/15 05:00 [medline]
PHST- 2003/07/02 05:00 [entrez]
AID - ncb1006 [pii]
AID - 10.1038/ncb1006 [doi]
PST - ppublish
SO  - Nat Cell Biol. 2003 Jul;5(7):668-74. doi: 10.1038/ncb1006.