Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.22 (
cdc2
)
8,319
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Chromatin remodeling is required for transcriptional activation and repression.
MRG15
(MORF4L1), a chromatin modulator, is a highly conserved protein and is present in complexes containing histone acetyltransferases (HATs) as well as histone deacetylases (HDACs). Loss of expression of
MRG15
in mice and Drosophila results in embryonic lethality and fibroblast and neural stem/progenitor cells cultured from Mrg15 null mouse embryos exhibit marked proliferative defects when compared with wild type cells. To determine the role of
MRG15
in cell cycle progression we performed chromatin immunoprecipitation with an antibody to
MRG15
on normal human fibroblasts as they entered the cell cycle from a quiescent state, and analyzed various cell cycle gene promoters. The results demonstrated a 3-fold increase in
MRG15
occupancy at the
cdc2
promoter during S phase of the cell cycle and a concomitant increase in acetylated histone H4. H4 lysine 12 was acetylated at 24 h post-serum stimulation while there was no change in acetylation of lysine 16. HDAC1 and 2 were decreased at this promoter during cell cycle progression. Over-expression of
MRG15
in HeLa cells activated a
cdc2
promoter-reporter construct in a dose-dependent manner, whereas knockdown of
MRG15
resulted in decreased promoter activity. In order to implicate HAT activity, we treated cells with the HAT inhibitor anacardic acid and determined that HAT inhibition results in loss of expression of
cdc2
mRNA. Further, chromatin immunoprecipitation with Tip60 localizes the protein to the same 110bp stretch of the
cdc2
promoter pulled down by
MRG15
. Additionally, we determined that cotransfection of
MRG15
with the known associated HAT Tip60 had a cooperative effect in activating the
cdc2
promoter. These results suggest that
MRG15
is acting in a HAT complex involving Tip60 to modify chromatin via acetylation of histone H4 at the
cdc2
promoter to activate transcription.
...
PMID:MRG15 activates the cdc2 promoter via histone acetylation in human cells. 2132 23
