TY - JOUR
T1 - A role for EZH2 in silencing of IFN-γ inducible MHC2TA transcription in uveal melanoma
AU - Holling, Tjadine M.
AU - Bergevoet, Marloes W.T.
AU - Wilson, Louis
AU - Van Eggermond, Marja C.J.A.
AU - Schooten, Erik
AU - Steenbergen, Renske D.M.
AU - Snijders, Peter J.F.
AU - Jager, Martine J.
AU - Van Den Elsen, Peter J.
PY - 2007/10/15
Y1 - 2007/10/15
N2 - We investigated the contribution of epigenetic mechanisms in MHC2TA transcriptional silencing in uveal melanoma. Although no correlation was observed between impaired CIITA transcript levels after IFN-γ induction and DNA methylation of MHC2TA promoter IV (CIITA-PIV), an association was found with high levels of trimethylated histone H3-lysine 27 (3Me-K27-H3) in CIITA-PIV chromatin. The 3Me-K27-H3 modification correlated with a strong reduction in RNA polymerase II-recruitment to CIITA-PIV. Interestingly, we observed that none of these epigenetic modifications affected recruitment of activating transcription factors to this promoter. Subsequently, we demonstrated the presence of the histone methyltransferase EZH2 in CIITA-PIV chromatin, which is known to be a component of the Polycomb repressive complex 2 and able to triple methylate histone H3-lysine 27. RNA interference-mediated down-regulation of EZH2 expression resulted in an increase in CIITA transcript levels after IFN-γ induction. Our data therefore reveal that EZH2 contributes to silencing of IFN-γ-inducible transcription of MHC2TA in uveal melanoma cells.
AB - We investigated the contribution of epigenetic mechanisms in MHC2TA transcriptional silencing in uveal melanoma. Although no correlation was observed between impaired CIITA transcript levels after IFN-γ induction and DNA methylation of MHC2TA promoter IV (CIITA-PIV), an association was found with high levels of trimethylated histone H3-lysine 27 (3Me-K27-H3) in CIITA-PIV chromatin. The 3Me-K27-H3 modification correlated with a strong reduction in RNA polymerase II-recruitment to CIITA-PIV. Interestingly, we observed that none of these epigenetic modifications affected recruitment of activating transcription factors to this promoter. Subsequently, we demonstrated the presence of the histone methyltransferase EZH2 in CIITA-PIV chromatin, which is known to be a component of the Polycomb repressive complex 2 and able to triple methylate histone H3-lysine 27. RNA interference-mediated down-regulation of EZH2 expression resulted in an increase in CIITA transcript levels after IFN-γ induction. Our data therefore reveal that EZH2 contributes to silencing of IFN-γ-inducible transcription of MHC2TA in uveal melanoma cells.
UR - http://www.scopus.com/inward/record.url?scp=38449110335&partnerID=8YFLogxK
M3 - Article
C2 - 17911618
SN - 0022-1767
VL - 179
SP - 5317
EP - 5325
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -