Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination

Gyu Lee Min; Raffaella Villa; Patrick Trojer; Jessica Norman; Kai Ping Yan; Danny Reinberg; Luciano Di Croce; Ramin Shiekhattar

doi:10.1126/science.1149042

Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination

Gyu Lee Min, Raffaella Villa, Patrick Trojer, Jessica Norman, Kai Ping Yan, Danny Reinberg, Luciano Di Croce, Ramin Shiekhattar

Research output: Contribution to journal › Article › peer-review

536 Scopus citations

Abstract

Methylation of histone H3 lysine 27 (H3K27) is a posttranslational modification that is highly correlated with genomic silencing. Here we show that human UTX, a member of the Jumonji C family of proteins, is a di- and trimethyl H3K27 demethylase. UTX occupies the promoters of HOX gene clusters and regulates their transcriptional output by modulating the recruitment of polycomb repressive complex 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 of the UTX complex to HOX genes results in H3K27 demethylation and a concomitant methylation of H3K4. Our results suggest a concerted mechanism for transcriptional activation in which cycles of H3K4 methylation by MLL2/3 are linked with the demethylation of H3K27 through UTX.

Original language	English (US)
Pages (from-to)	447-450
Number of pages	4
Journal	Science
Volume	318
Issue number	5849
DOIs	https://doi.org/10.1126/science.1149042
State	Published - Oct 19 2007
Externally published	Yes

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title = "Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination",

abstract = "Methylation of histone H3 lysine 27 (H3K27) is a posttranslational modification that is highly correlated with genomic silencing. Here we show that human UTX, a member of the Jumonji C family of proteins, is a di- and trimethyl H3K27 demethylase. UTX occupies the promoters of HOX gene clusters and regulates their transcriptional output by modulating the recruitment of polycomb repressive complex 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 of the UTX complex to HOX genes results in H3K27 demethylation and a concomitant methylation of H3K4. Our results suggest a concerted mechanism for transcriptional activation in which cycles of H3K4 methylation by MLL2/3 are linked with the demethylation of H3K27 through UTX.",

author = "Min, {Gyu Lee} and Raffaella Villa and Patrick Trojer and Jessica Norman and Yan, {Kai Ping} and Danny Reinberg and {Di Croce}, Luciano and Ramin Shiekhattar",

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T1 - Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination

AU - Min, Gyu Lee

AU - Villa, Raffaella

AU - Trojer, Patrick

AU - Norman, Jessica

AU - Yan, Kai Ping

AU - Reinberg, Danny

AU - Di Croce, Luciano

AU - Shiekhattar, Ramin

PY - 2007/10/19

Y1 - 2007/10/19

N2 - Methylation of histone H3 lysine 27 (H3K27) is a posttranslational modification that is highly correlated with genomic silencing. Here we show that human UTX, a member of the Jumonji C family of proteins, is a di- and trimethyl H3K27 demethylase. UTX occupies the promoters of HOX gene clusters and regulates their transcriptional output by modulating the recruitment of polycomb repressive complex 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 of the UTX complex to HOX genes results in H3K27 demethylation and a concomitant methylation of H3K4. Our results suggest a concerted mechanism for transcriptional activation in which cycles of H3K4 methylation by MLL2/3 are linked with the demethylation of H3K27 through UTX.

AB - Methylation of histone H3 lysine 27 (H3K27) is a posttranslational modification that is highly correlated with genomic silencing. Here we show that human UTX, a member of the Jumonji C family of proteins, is a di- and trimethyl H3K27 demethylase. UTX occupies the promoters of HOX gene clusters and regulates their transcriptional output by modulating the recruitment of polycomb repressive complex 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 of the UTX complex to HOX genes results in H3K27 demethylation and a concomitant methylation of H3K4. Our results suggest a concerted mechanism for transcriptional activation in which cycles of H3K4 methylation by MLL2/3 are linked with the demethylation of H3K27 through UTX.

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