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Demethylation of H3K27 Regulates Polycomb Recruitment and H2A Ubiquitination
Min Gyu Lee,1
Raffaella Villa,2
Patrick Trojer,3
Jessica Norman,1
Kai-Ping Yan,1
Danny Reinberg,3
Luciano Di Croce,2
Ramin Shiekhattar1,2*
Abstract:
Methylation of histone H3 lysine 27 (H3K27) is a posttranslationalmodification that is highly correlated with genomic silencing.Here we show that human UTX, a member of the Jumonji C familyof proteins, is a di- and trimethyl H3K27 demethylase. UTX occupiesthe promoters of HOX gene clusters and regulates their transcriptionaloutput by modulating the recruitment of polycomb repressivecomplex 1 and the monoubiquitination of histone H2A. Moreover,UTX associates with mixed-lineage leukemia (MLL) 2/3 complexes,and during retinoic acid signaling events, the recruitment ofthe UTX complex to HOX genes results in H3K27 demethylationand a concomitant methylation of H3K4. Our results suggest aconcerted mechanism for transcriptional activation in whichcycles of H3K4 methylation by MLL2/3 are linked with the demethylationof H3K27 through UTX.
1 The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA. 2 Institució Catalana de Recerca i Estudis Avançats and Centre de Regulació Genòmica, Barcelona, Spain. 3 Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
* To whom correspondence should be addressed. E-mail: ramin.shiekhattar{at}crg.es
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