PMID- 15674423
OWN - NLM
STAT- MEDLINE
DCOM- 20050329
LR  - 20130304
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 19
IP  - 3
DP  - 2005 Mar
TI  - Epigenetic changes in the repression and induction of asparagine synthetase in 
      human leukemic cell lines.
PG  - 420-6
AB  - In common with certain other lymphoid neoplasms, cells of the human lymphocytic 
      leukemia lines 1873 and 1929 are asparagine (ASN) auxotrophs. Asparagine 
      synthetase (ASY), which is a housekeeping gene, is repressed and the promoting 
      region of the gene is highly methylated. We now demonstrate in these cells 
      multiple levels in control of the expression of this gene, in a system of 
      cocultivation with macrophages and other cell types. In this system, mediated by 
      cell-to-cell contact, ASY becomes expressed by the leukemic cells and they become 
      prototrophic. Demethylation of ASY occurs; it follows expression and is permanent 
      over multiple cell generations, but the cells return to auxotrophy with rapid 
      repression of ASY on removal from cell contact. With ASY expression, the 
      associated histone H3 at lysine position 9 (H3K9) becomes acetylated and H3K4, 
      methylated. In contrast to other systems, H3K9 methylation does not characterize 
      the repressed state. The changes leading from repression to induction of ASY and 
      demethylation parallel the physiological changes specific to functional 
      maturation of normal lymphoid precursors. The lability of expression of ASY has 
      potential significance in determining the sensitivity of leukemic cells to 
      L-asparaginase.
FAU - Ding, Y
AU  - Ding Y
AD  - Department of Pathology, North Shore University Hospital, Manhasset, NY 11030, 
      USA.
FAU - Li, Z
AU  - Li Z
FAU - Broome, J D
AU  - Broome JD
LA  - eng
PT  - Journal Article
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Histones)
RN  - 7006-34-0 (Asparagine)
RN  - EC 6.3.1.1 (Aspartate-Ammonia Ligase)
SB  - IM
EIN - Leukemia. 2005 Jun;19(6):1108
MH  - Acetylation
MH  - Animals
MH  - Asparagine/metabolism
MH  - Aspartate-Ammonia Ligase/biosynthesis/*genetics/metabolism
MH  - Cell Division/physiology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Enzyme Induction/genetics
MH  - *Epigenesis, Genetic
MH  - Gene Silencing
MH  - Histones/metabolism
MH  - Humans
MH  - Leukemia/*enzymology/*genetics
MH  - Macrophages/cytology
MH  - Methylation
MH  - Mice
MH  - Promoter Regions, Genetic
EDAT- 2005/01/28 09:00
MHDA- 2005/03/30 09:00
CRDT- 2005/01/28 09:00
PHST- 2005/01/28 09:00 [pubmed]
PHST- 2005/03/30 09:00 [medline]
PHST- 2005/01/28 09:00 [entrez]
AID - 2403639 [pii]
AID - 10.1038/sj.leu.2403639 [doi]
PST - ppublish
SO  - Leukemia. 2005 Mar;19(3):420-6. doi: 10.1038/sj.leu.2403639.