Oxygenase catalyzed 5-methylcytosine hydroxylation. by Loenarz, C, Schofield, C

“…This discovery has potential far-reaching implications for epigenetic regulation and will stimulate efforts to identify new nucleic acid modifications.…”

Studies of histone modifications in yeast and humans by Hsu, K

“…<p>Epigenetic regulation is a complex biological process that has influence on the structure of chromatin and impacts on the regulation of DNA-associated events, including transcription, DNA replication, and DNA damage repair. …”

Generation of a synthetic GlcNAcylated nucleosome reveals regulation of stability by H2A-Thr101 GlcNAcylation by Lercher, L, Raj, R, Patel, N, Price, J, Mohammed, S, Robinson, C, Schofield, C, Davis, B

“…The results suggest that a plausible molecular basis for one role of histone O-GlcNAcylation in epigenetic regulation is to lower the barrier for RNA polymerase passage and hence increase transcription.…”

Targeting histone lysine demethylases - Progress, challenges, and the future. by Thinnes, C, England, K, Kawamura, A, Chowdhury, R, Schofield, C, Hopkinson, R

“…Modulation of histone methylation status is proposed to be important in epigenetic regulation and has substantial medicinal potential for the treatment of diseases including cancer and genetic disorders. …”

Investigations on the oxygen dependence of a 2-oxoglutarate histone demethylase. by Sánchez-Fernández, E, Tarhonskaya, H, Al-Qahtani, K, Hopkinson, R, McCullagh, J, Schofield, C, Flashman, E

“…Histone N(ϵ)-methyl lysine demethylases are important in epigenetic regulation. KDM4E (histone lysine demethylase 4E) is a representative member of the large Fe(II)/2-oxoglutarate- dependent family of human histone demethylases. …”

Structural and functional studies of chromatin modifying enzymes by Walport, L

“…<p>Epigenetic regulation is a complex process involving the interplay of multiple different cellular factors. …”

A miniaturized screen for inhibitors of Jumonji histone demethylases. by Sakurai, M, Rose, N, Schultz, L, Quinn, A, Jadhav, A, Ng, S, Oppermann, U, Schofield, C, Simeonov, A

“…2-Oxoglutarate- and Fe(ii)-dependent oxygenases are a major class of N(epsilon)-methyl lysine demethylases that are involved in epigenetic regulation. Assays suitable for implementation in a high-throughput manner have been lacking for these enzymes. …”

Identifying small molecule binding sites for epigenetic proteins at domain-domain interfaces by Brennan, P, Bowkett, D, Talon, R, Tallant, C, Schofield, C, Bruton, G, Von Delft, F, Knapp, S

“…As many of the proteins in epigenetic regulation have multiple domains there are opportunities for designing inhibitors that bind at a domain‐domain interface which provide a more suitable interaction pocket. …”

Adventures in defining roles of oxygenases in the regulation of protein biosynthesis by Walport, L, Schofield, C

“…In humans, 2OG oxygenases have been found to have roles in small molecule metabolism, as well as in the epigenetic regulation of protein and nucleic acid biosynthesis and function. …”

Hypoxia and hypoxia mimetics differentially modulate histone post-translational modifications by Hsu, K-F, Wilkins, S, Hopkinson, R, Sekirnik, R, Flashman, E, Kawamura, A, McCullagh, J, Walport, L, Schofield, C

“…Post-translational modifications (PTMs) to the tails of the core histone proteins are critically involved in epigenetic regulation. Hypoxia affects histone modifications by altering the activities of histone-modifying enzymes and the levels of hypoxia-inducible factor (HIF) isoforms. …”

Regulation of Jumonji-domain-containing histone demethylases by hypoxia-inducible factor (HIF)-1alpha. by Pollard, P, Loenarz, C, Mole, D, McDonough, M, Gleadle, J, Schofield, C, Ratcliffe, P

“…Given the importance of histone methylation status in defining patterns of gene expression under different physiological and pathophysiological conditions, these findings predict a role for the HIF system in epigenetic regulation.…”

The broad spectrum 2-oxoglutarate oxygenase inhibitor N-oxalylglycine is present in rhubarb and spinach leaves by Al-Qahtani, K, Jabeen, B, Sekirnik, R, Riaz, N, Claridge, T, Schofield, C, McCullagh, J

“…These enzymes are of significant biomedicinal interest because of their roles in hypoxic signaling and epigenetic regulation. Synthetic N-oxalylglycine (NOG) has been identified as a broad-spectrum 2OG oxygenase inhibitor and is currently widely used in studies on the hypoxic response and chromatin modifications in animals. …”

A cell-permeable ester derivative of the JmjC histone demethylase inhibitor IOX1. by Schiller, R, Scozzafava, G, Tumber, A, Wickens, JR, Bush, J, Rai, G, Lejeune, C, Choi, H, Yeh, T, Chan, M, Mott, B, McCullagh, J, Maloney, D, Schofield, C, Kawamura, A

“…The n-octyl ester of IOX1 should find utility as a starting point for the development of JmjC inhibitors and as a use as a cell-permeable tool compound for studies investigating the roles of 2OG oxygenases in epigenetic regulation.…”

A miniaturized screen for inhibitors of Jumonji histone demethylases. by Sakurai, M, Rose, N, Schultz, L, Quinn, A, Jadhav, A, Ng, S, Oppermann, U, Schofield, C, Simeonov, A

“…2-Oxoglutarate- and Fe(ii)-dependent oxygenases are a major class of N(epsilon)-methyl lysine demethylases that are involved in epigenetic regulation. Assays suitable for implementation in a high-throughput manner have been lacking for these enzymes. …”

Crystal structures of histone demethylase JMJD2A reveal basis for substrate specificity. by Ng, S, Kavanagh, K, McDonough, M, Butler, D, Pilka, E, Lienard, B, Bray, J, Savitsky, P, Gileadi, O, von Delft, F, Rose, N, Offer, J, Scheinost, J, Borowski, T, Sundstrom, M, Schofield, C, Oppermann, U

“…Post-translational histone modification has a fundamental role in chromatin biology and is proposed to constitute a 'histone code' in epigenetic regulation. Differential methylation of histone H3 and H4 lysyl residues regulates processes including heterochromatin formation, X-chromosome inactivation, genome imprinting, DNA repair and transcriptional regulation. …”

Investigations on small molecule inhibitors targeting the histone H3K4 tri-methyllysine binding PHD-finger of JmjC histone demethylases by Bhushan, B, Erdmann, A, Zhang, Y, Belle, R, Johannson, C, Oppermann, U, Hopkinson, R, Schofield, C, Kawamura, A

“…Plant homeodomain (PHD) containing proteins are important epigenetic regulators and are of interest as potential drug targets. …”