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

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518 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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Min, G. L., Villa, R., Trojer, P., Norman, J., Yan, K. P., Reinberg, D., Di Croce, L., & Shiekhattar, R. (2007). Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination. Science, 318(5849), 447-450. https://doi.org/10.1126/science.1149042

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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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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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