Inhibition of demethylases by GSK-J1/J4

TY - JOUR

T1 - Inhibition of demethylases by GSK-J1/J4

AU - Heinemann, Bo

AU - Nielsen, Jesper Morten

AU - Hudlebusch, Heidi Rye

AU - Lees, Michael J

AU - Larsen, Dorthe Vang

AU - Boesen, Thomas

AU - Labelle, Marc

AU - Gerlach, Lars-Ole

AU - Birk, Peter

AU - Helin, Kristian

PY - 2014/10/2

Y1 - 2014/10/2

N2 - Arising from L. Kruidenier et al. Nature 488, 404-408 (2012); doi:10.1038/nature11262The recent publication of the first highly potent and specific inhibitor GSK-J1/J4 of the H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A provides a potential tool compound for this histone demethylase subfamily. This inhibitor was used in tissue culture assays to conclude that the catalytic activities of the KDM6 proteins are required in inflammatory responses; the generation of the inhibitor is intriguing, because it provides a strategy for generating sub-type-specific inhibitors of the 27-member Jumonji family and for the future treatment of various types of disease. Here we show that the inhibitor is not specific for the H3K27me3/me2-demethylase subfamily in vitro and in tissue culture assays. Thus, the inhibitor cannot be used alone for drawing conclusions regarding the specific role of H3K27me3/me2-demethylase activity in biological processes or disease. There is a Reply to this Brief Communications Arising by Kruidenier et al. Nature 514, http://dx.doi.org/10.1038/nature13689 (2014).

AB - Arising from L. Kruidenier et al. Nature 488, 404-408 (2012); doi:10.1038/nature11262The recent publication of the first highly potent and specific inhibitor GSK-J1/J4 of the H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A provides a potential tool compound for this histone demethylase subfamily. This inhibitor was used in tissue culture assays to conclude that the catalytic activities of the KDM6 proteins are required in inflammatory responses; the generation of the inhibitor is intriguing, because it provides a strategy for generating sub-type-specific inhibitors of the 27-member Jumonji family and for the future treatment of various types of disease. Here we show that the inhibitor is not specific for the H3K27me3/me2-demethylase subfamily in vitro and in tissue culture assays. Thus, the inhibitor cannot be used alone for drawing conclusions regarding the specific role of H3K27me3/me2-demethylase activity in biological processes or disease. There is a Reply to this Brief Communications Arising by Kruidenier et al. Nature 514, http://dx.doi.org/10.1038/nature13689 (2014).

U2 - 10.1038/nature13688

DO - 10.1038/nature13688

M3 - Journal article

C2 - 25279926

SN - 0028-0836

VL - 514

SP - E1-2

JO - Nature

JF - Nature

IS - 7520

ER -