TY - JOUR
T1 - OTX2 regulates expression of DOPAchrome tautomerase in human retinal pigment epithelium
AU - Takeda, Kazuhisa
AU - Yokoyama, Satoru
AU - Yasumoto, Ken Ichi
AU - Saito, Hideo
AU - Udono, Tetsuo
AU - Takahashi, Kazuhiro
AU - Shibahara, Shigeki
N1 - Funding Information:
We thank A. Ruiz i Altaba for anti-OTX2 antibody, V. Hearing for anti-DCT antibody, D.E. Fisher for anti-MITF antibody, and M. Yoshizawa for technical assistance. We also thank H. Yamamoto and I. Yajima for helpful discussion. This work was supported in part by Grants-in-Aid for Scientific Research (C) and for Exploratory Research from the Ministry of Education, Science, Sports and Culture of Japan. This work was also supported in part by the grants provided by Uehara Memorial Foundation, the Cosmetology Research Foundation, and the SHISEIDO Grant for Skin Aging Research (SRG No. 10258).
PY - 2003/1/24
Y1 - 2003/1/24
N2 - Otx2 is a member of homeodomain-containing transcription factors and is essential for eye morphogenesis in mice. Here we show the expression of OTX2, the human counterpart of Otx2, in cell lines of retinal pigment epithelium (RPE) and in Y79 retinoblastoma cells that exhibit the property of presumptive RPE. These RPE cells express DOPAchrome tautomerase (DCT) that is an enzyme involved in melanin biosynthesis. DCT may contribute to the homeostasis of RPE by detoxifying DOPA-derived metabolites. OTX2 binds to the DCT gene promoter in vivo, as judged by chromatin immunoprecipitation assays. Furthermore, repression of endogenous OTX2 expression in Y79 cells by an anti-sense OTX2 oligonucleotide resulted in the decrease of DCT protein contents. Transient expression assays revealed that OTX2 activated the DCT gene promoter through the OTX-2-binding site in an RPE-specific manner. Therefore, OTX2 may regulate RPE-specific target genes, such as DCT, thereby maintaining the homeostasis of RPE.
AB - Otx2 is a member of homeodomain-containing transcription factors and is essential for eye morphogenesis in mice. Here we show the expression of OTX2, the human counterpart of Otx2, in cell lines of retinal pigment epithelium (RPE) and in Y79 retinoblastoma cells that exhibit the property of presumptive RPE. These RPE cells express DOPAchrome tautomerase (DCT) that is an enzyme involved in melanin biosynthesis. DCT may contribute to the homeostasis of RPE by detoxifying DOPA-derived metabolites. OTX2 binds to the DCT gene promoter in vivo, as judged by chromatin immunoprecipitation assays. Furthermore, repression of endogenous OTX2 expression in Y79 cells by an anti-sense OTX2 oligonucleotide resulted in the decrease of DCT protein contents. Transient expression assays revealed that OTX2 activated the DCT gene promoter through the OTX-2-binding site in an RPE-specific manner. Therefore, OTX2 may regulate RPE-specific target genes, such as DCT, thereby maintaining the homeostasis of RPE.
KW - Differentiation
KW - DOPA
KW - DOPAchrome tautomerase
KW - Melanin
KW - OTX2
KW - Retinal pigment epithelium
KW - Retinoblastoma
KW - Transcription factor
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U2 - 10.1016/S0006-291X(02)02934-0
DO - 10.1016/S0006-291X(02)02934-0
M3 - Article
C2 - 12559959
AN - SCOPUS:0037462932
SN - 0006-291X
VL - 300
SP - 908
EP - 914
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -