BACKGROUND: Disease pathogenesis may result from genetic alterations
and/or a more diverse group of epigenetic changes. While events such
as DNA methylation are well established, there is significant interest
in nucleosome remodeling, RNA interference and histone modifications,
as mechanisms that underlie epigenetic effects. While genetic mutations
are permanent, epigenetic changes can be transitory. The potential
to reverse epigenetic changes has led to the development of therapeutic
strategies targeting chromatin-modifying enzymes. OBJECTIVE: To review
the roles of chromatin-modifying enzymes in gene regulation and to
highlight their potentials as therapeutic targets. Methods: This
review is based on recently published literature and online resources.
RESULTS/CONCLUSION: This paper focuses on enzymes responsible for
histone acetylation, deacetylation, methylation and demethylation,
and their potential as targets for epigenetic therapies. A subsequent
paper will do the same for enzymes responsible for histone phosphorylation,
ubiquitylation, SUMOylation and poly-ADP-ribosylation as well as
ATP-dependent nucleosome remodeling.
%0 Journal Article
%1 Keppler2008a
%A Keppler, Brian R.
%A Archer, Trevor K.
%D 2008
%J Expert Opin Ther Targets
%K Animals Chromatin,_metabolism Enzymes,_metabolism Histone_Acetyltransferases,_antagonists_/\&/_inhibitors/metabolism Histone_Deacetylases,_antagonists_/\&/_inhibitors/metabolism Humans Protein_Methyltransferases,_antagonists_/\&/_inhibitors/metabolism
%N 10
%P 1301-1312
%R 10.1517/14728222.12.10.1301
%T Chromatin-modifying enzymes as therapeutic targets--Part 1.
%U http://dx.doi.org/10.1517/14728222.12.10.1301
%V 12
%X BACKGROUND: Disease pathogenesis may result from genetic alterations
and/or a more diverse group of epigenetic changes. While events such
as DNA methylation are well established, there is significant interest
in nucleosome remodeling, RNA interference and histone modifications,
as mechanisms that underlie epigenetic effects. While genetic mutations
are permanent, epigenetic changes can be transitory. The potential
to reverse epigenetic changes has led to the development of therapeutic
strategies targeting chromatin-modifying enzymes. OBJECTIVE: To review
the roles of chromatin-modifying enzymes in gene regulation and to
highlight their potentials as therapeutic targets. Methods: This
review is based on recently published literature and online resources.
RESULTS/CONCLUSION: This paper focuses on enzymes responsible for
histone acetylation, deacetylation, methylation and demethylation,
and their potential as targets for epigenetic therapies. A subsequent
paper will do the same for enzymes responsible for histone phosphorylation,
ubiquitylation, SUMOylation and poly-ADP-ribosylation as well as
ATP-dependent nucleosome remodeling.
@article{Keppler2008a,
abstract = {BACKGROUND: Disease pathogenesis may result from genetic alterations
and/or a more diverse group of epigenetic changes. While events such
as DNA methylation are well established, there is significant interest
in nucleosome remodeling, RNA interference and histone modifications,
as mechanisms that underlie epigenetic effects. While genetic mutations
are permanent, epigenetic changes can be transitory. The potential
to reverse epigenetic changes has led to the development of therapeutic
strategies targeting chromatin-modifying enzymes. OBJECTIVE: To review
the roles of chromatin-modifying enzymes in gene regulation and to
highlight their potentials as therapeutic targets. Methods: This
review is based on recently published literature and online resources.
RESULTS/CONCLUSION: This paper focuses on enzymes responsible for
histone acetylation, deacetylation, methylation and demethylation,
and their potential as targets for epigenetic therapies. A subsequent
paper will do the same for enzymes responsible for histone phosphorylation,
ubiquitylation, SUMOylation and poly-ADP-ribosylation as well as
ATP-dependent nucleosome remodeling.},
added-at = {2010-01-26T20:35:53.000+0100},
author = {Keppler, Brian R. and Archer, Trevor K.},
biburl = {https://www.bibsonomy.org/bibtex/26e8d8107ad9d90784f10164cb9db7f8c/denilw},
doi = {10.1517/14728222.12.10.1301},
institution = {National Institute of Environmental Health Sciences, National Institutes
of Health, North Carolina 27709, USA.},
interhash = {3bee2186c1d4d6743cf8c7f63c9f5369},
intrahash = {6e8d8107ad9d90784f10164cb9db7f8c},
journal = {Expert Opin Ther Targets},
keywords = {Animals Chromatin,_metabolism Enzymes,_metabolism Histone_Acetyltransferases,_antagonists_/\&/_inhibitors/metabolism Histone_Deacetylases,_antagonists_/\&/_inhibitors/metabolism Humans Protein_Methyltransferases,_antagonists_/\&/_inhibitors/metabolism},
month = Oct,
number = 10,
owner = {denilw},
pages = {1301-1312},
pmid = {18781828},
timestamp = {2010-01-26T20:36:00.000+0100},
title = {Chromatin-modifying enzymes as therapeutic targets{--}Part 1.},
url = {http://dx.doi.org/10.1517/14728222.12.10.1301},
volume = 12,
year = 2008
}