The Oncoprotein Set/TAF-1β, an Inhibitor of Histone Acetyltransferase, Inhibits Active Demethylation of DNA, Integrating DNA Methylation and Transcriptional Silencing
Histone hypoacetylation and DNA hypermethylation are hallmarks of gene silencing. Although a role for DNA methylation in regulating histone acetylation has been established, it is not clear how and whether epigenetic histone markings influence DNA modifications in transcriptional silencing. We have...
Saved in:
Published in | The Journal of biological chemistry Vol. 277; no. 28; p. 25026 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
American Society for Biochemistry and Molecular Biology
12.07.2002
|
Online Access | Get full text |
Cover
Loading…
Summary: | Histone hypoacetylation and DNA hypermethylation are hallmarks of gene silencing. Although a role for DNA methylation in regulating
histone acetylation has been established, it is not clear how and whether epigenetic histone markings influence DNA modifications
in transcriptional silencing. We have previously shown that induction of histone acetylation by trichostatin A promotes demethylation
of ectopically methylated DNA (Cervoni, N., and Szyf, M. (2001) J. Biol. Chem. 276, 40778â40787). The oncoprotein Set/TAF-Iβ is a subunit of the recently identified inhibitor of acetyltransferases complex
that inhibits histone acetylation by binding to and masking histone acetyltransferase targets (Seo, S. B., McNamara, P., Heo,
S., Turner, A., Lane, W. S., and Chakravarti, D. (2001) Cell 104, 119â130). We show here that the overexpression of Set/TAF-Iβ, whose expression is up-regulated in multiple tumor tissues,
inhibits demethylation of ectopically methylated DNA resulting in gene silencing. Overexpression of a mutant Set/TAF-Iβ that
does not inhibit histone acetylation is defective in inhibiting DNA demethylation. Taken together, these results are consistent
with a novel regulatory role for Set/TAF-Iβ, integrating epigenetic states of histones and DNA in gene regulation and provide
a new mechanism that can explain how hypermethylation of specific regions might come about by inhibition of demethylation
in cancer cells. |
---|---|
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M202256200 |