PMID- 19707557
OWN - NLM
STAT- MEDLINE
DCOM- 20100119
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 4
IP  - 8
DP  - 2009 Aug 26
TI  - Disruption of histone modification and CARM1 recruitment by arsenic represses 
      transcription at glucocorticoid receptor-regulated promoters.
PG  - e6766
LID - 10.1371/journal.pone.0006766 [doi]
LID - e6766
AB  - Chronic exposure to inorganic arsenic (iAs) found in the environment is one of 
      the most significant and widespread environmental health risks in the U.S. and 
      throughout the world. It is associated with a broad range of health effects from 
      cancer to diabetes as well as reproductive and developmental anomalies. This 
      diversity of diseases can also result from disruption of metabolic and other 
      cellular processes regulated by steroid hormone receptors via aberrant 
      transcriptional regulation. Significantly, exposure to iAs inhibits steroid 
      hormone-mediated gene activation. iAs exposure is associated with disease, but is 
      also used therapeutically to treat specific cancers complicating an understanding 
      of iAs action. Transcriptional activation by steroid hormone receptors is 
      accompanied by changes in histone and non-histone protein post-translational 
      modification (PTM) that result from the enzymatic activity of coactivator and 
      corepressor proteins such as GRIP1 and CARM1. This study addresses how iAs 
      represses steroid receptor-regulated gene transcription. PTMs on histones H3 and 
      H4 at the glucocorticoid receptor (GR)-activated mouse mammary tumor virus (MMTV) 
      promoter were identified by chromatin immunoprecipitation analysis following 
      exposure to steroid hormone+/-iAs. Histone H3K18 and H3R17 amino acid residues 
      had significantly different patterns of PTMs after treatment with iAs. Promoter 
      interaction of the coactivator CARM1 was disrupted, but the interaction of GRIP1, 
      a p160 coactivator through which CARM1 interacts with a promoter, was intact. 
      Over-expression of CARM1 was able to fully restore and GRIP1 partially restored 
      iAs-repressed transcription indicating that these coactivators are functionally 
      associated with iAs-mediated transcriptional repression. Both are essential for 
      robust transcription at steroid hormone regulated genes and both are associated 
      with disease when inappropriately expressed. We postulate that iAs effects on 
      CARM1 and GRIP1 may underlie some of its therapeutic effects and as well be 
      associated with its toxic effects.
FAU - Barr, Fiona D
AU  - Barr FD
AD  - Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire, USA.
FAU - Krohmer, Lori J
AU  - Krohmer LJ
FAU - Hamilton, Joshua W
AU  - Hamilton JW
FAU - Sheldon, Lynn A
AU  - Sheldon LA
LA  - eng
GR  - P42 ES007373/ES/NIEHS NIH HHS/United States
GR  - R01 ES013168/ES/NIEHS NIH HHS/United States
GR  - ES013168/ES/NIEHS NIH HHS/United States
GR  - ES007373/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090826
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Histones)
RN  - 0 (Receptors, Glucocorticoid)
RN  - EC 2.1.1.319 (Protein-Arginine N-Methyltransferases)
RN  - EC 2.1.1.319 (coactivator-associated arginine methyltransferase 1)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
RN  - N712M78A8G (Arsenic)
SB  - IM
MH  - Animals
MH  - Arsenic/*pharmacology
MH  - Cell Line, Tumor
MH  - Chloramphenicol O-Acetyltransferase/genetics
MH  - Chromatin Immunoprecipitation
MH  - Electrophoretic Mobility Shift Assay
MH  - Histones/*metabolism
MH  - Mice
MH  - Polymerase Chain Reaction
MH  - *Promoter Regions, Genetic
MH  - Protein-Arginine N-Methyltransferases/*metabolism
MH  - Receptors, Glucocorticoid/*physiology
MH  - Transcription, Genetic/*drug effects
PMC - PMC2727952
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/08/27 09:00
MHDA- 2010/01/20 06:00
PMCR- 2009/08/26
CRDT- 2009/08/27 09:00
PHST- 2009/04/22 00:00 [received]
PHST- 2009/07/31 00:00 [accepted]
PHST- 2009/08/27 09:00 [entrez]
PHST- 2009/08/27 09:00 [pubmed]
PHST- 2010/01/20 06:00 [medline]
PHST- 2009/08/26 00:00 [pmc-release]
AID - 09-PONE-RA-09922R1 [pii]
AID - 10.1371/journal.pone.0006766 [doi]
PST - epublish
SO  - PLoS One. 2009 Aug 26;4(8):e6766. doi: 10.1371/journal.pone.0006766.