Human UTY(KDM6C) is a male-specific Nϵ-methyl lysyl demethylase.
The Jumonji C lysine demethylases (KDMs) are 2-oxoglutarate- and Fe(II)-dependent oxygenases. KDM6A (UTX) and KDM6B (JMJD3) are KDM6 subfamily members that catalyze demethylation of N(ϵ)-methylated histone 3 lysine 27 (H3K27), a mark important for transcriptional repression. Despite reports stating...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2014
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| _version_ | 1826288396073435136 |
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| author | Walport, L Hopkinson, R Vollmar, M Madden, S Gileadi, C Oppermann, U Schofield, C Johansson, C |
| author_facet | Walport, L Hopkinson, R Vollmar, M Madden, S Gileadi, C Oppermann, U Schofield, C Johansson, C |
| author_sort | Walport, L |
| collection | OXFORD |
| description | The Jumonji C lysine demethylases (KDMs) are 2-oxoglutarate- and Fe(II)-dependent oxygenases. KDM6A (UTX) and KDM6B (JMJD3) are KDM6 subfamily members that catalyze demethylation of N(ϵ)-methylated histone 3 lysine 27 (H3K27), a mark important for transcriptional repression. Despite reports stating that UTY(KDM6C) is inactive as a KDM, we demonstrate by biochemical studies, employing MS and NMR, that UTY(KDM6C) is an active KDM. Crystallographic analyses reveal that the UTY(KDM6C) active site is highly conserved with those of KDM6B and KDM6A. UTY(KDM6C) catalyzes demethylation of H3K27 peptides in vitro, analogously to KDM6B and KDM6A, but with reduced activity, due to point substitutions involved in substrate binding. The results expand the set of human KDMs and will be of use in developing selective KDM inhibitors. |
| first_indexed | 2024-03-07T02:12:57Z |
| format | Journal article |
| id | oxford-uuid:a148f9ca-d821-4a40-9c3c-b7af20587d13 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:12:57Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:a148f9ca-d821-4a40-9c3c-b7af20587d132022-03-27T02:12:11ZHuman UTY(KDM6C) is a male-specific Nϵ-methyl lysyl demethylase.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a148f9ca-d821-4a40-9c3c-b7af20587d13EnglishSymplectic Elements at Oxford2014Walport, LHopkinson, RVollmar, MMadden, SGileadi, COppermann, USchofield, CJohansson, CThe Jumonji C lysine demethylases (KDMs) are 2-oxoglutarate- and Fe(II)-dependent oxygenases. KDM6A (UTX) and KDM6B (JMJD3) are KDM6 subfamily members that catalyze demethylation of N(ϵ)-methylated histone 3 lysine 27 (H3K27), a mark important for transcriptional repression. Despite reports stating that UTY(KDM6C) is inactive as a KDM, we demonstrate by biochemical studies, employing MS and NMR, that UTY(KDM6C) is an active KDM. Crystallographic analyses reveal that the UTY(KDM6C) active site is highly conserved with those of KDM6B and KDM6A. UTY(KDM6C) catalyzes demethylation of H3K27 peptides in vitro, analogously to KDM6B and KDM6A, but with reduced activity, due to point substitutions involved in substrate binding. The results expand the set of human KDMs and will be of use in developing selective KDM inhibitors. |
| spellingShingle | Walport, L Hopkinson, R Vollmar, M Madden, S Gileadi, C Oppermann, U Schofield, C Johansson, C Human UTY(KDM6C) is a male-specific Nϵ-methyl lysyl demethylase. |
| title | Human UTY(KDM6C) is a male-specific Nϵ-methyl lysyl demethylase. |
| title_full | Human UTY(KDM6C) is a male-specific Nϵ-methyl lysyl demethylase. |
| title_fullStr | Human UTY(KDM6C) is a male-specific Nϵ-methyl lysyl demethylase. |
| title_full_unstemmed | Human UTY(KDM6C) is a male-specific Nϵ-methyl lysyl demethylase. |
| title_short | Human UTY(KDM6C) is a male-specific Nϵ-methyl lysyl demethylase. |
| title_sort | human uty kdm6c is a male specific nϵ methyl lysyl demethylase |
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