%0 Book Section %1 JELTSCH20243 %A Jeltsch, Albert %A Choudalakis, Michel %A Dukatz, Michael %A Kunert, Stefan %B Chromatin Readers in Health and Disease %D 2024 %E Binda, Olivier %I Academic Press %K %P 3-11 %R https://doi.org/10.1016/B978-0-12-823376-4.00002-1 %T Chapter 1 - ADD domains—A regulatory hub in chromatin biology and disease %U https://www.sciencedirect.com/science/article/pii/B9780128233764000021 %V 35 %X ADD domains have been identified in the DNMT3A and DNMT3B DNA methyltransferases, the DNMT3L regulator of DNMT3 enzymes, and the ATRX SNF2 family chromatin remodeler. The domain folds into a GATA-like zinc finger, a PHD domain, and a carboxy-terminal alpha-helix. It binds to histone H3 amino-terminal tail peptides, if they are unmethylated at K4. This interaction contributes to the subnuclear localization of DNMT3 proteins and to the global anticorrelation of DNA methylation and H3K4me2/3. Due to the presence of an additional binding pocket for trimethyllysine, the ATRX ADD domain binds to H3 tail peptides unmodified at K4 and trimethylated at K9, and this property contributes to the heterochromatic localization of the ATRX protein. ADD domains are a hub for protein-protein interactions, and they are involved in the allosteric regulation of DNMT3A activity. Mutations in the ADD domain have been associated with the alpha-thalassemia mental retardation X-linked syndrome in the case of the ATRX protein and with cancer and the Tatton-Brown-Rahman overgrowth syndrome in the case of DNMT3A. %@ 978-0-12-823376-4

@incollection{JELTSCH20243, abstract = {ADD domains have been identified in the DNMT3A and DNMT3B DNA methyltransferases, the DNMT3L regulator of DNMT3 enzymes, and the ATRX SNF2 family chromatin remodeler. The domain folds into a GATA-like zinc finger, a PHD domain, and a carboxy-terminal alpha-helix. It binds to histone H3 amino-terminal tail peptides, if they are unmethylated at K4. This interaction contributes to the subnuclear localization of DNMT3 proteins and to the global anticorrelation of DNA methylation and H3K4me2/3. Due to the presence of an additional binding pocket for trimethyllysine, the ATRX ADD domain binds to H3 tail peptides unmodified at K4 and trimethylated at K9, and this property contributes to the heterochromatic localization of the ATRX protein. ADD domains are a hub for protein-protein interactions, and they are involved in the allosteric regulation of DNMT3A activity. Mutations in the ADD domain have been associated with the alpha-thalassemia mental retardation X-linked syndrome in the case of the ATRX protein and with cancer and the Tatton-Brown-Rahman overgrowth syndrome in the case of DNMT3A.}, added-at = {2024-01-13T11:21:22.000+0100}, author = {Jeltsch, Albert and Choudalakis, Michel and Dukatz, Michael and Kunert, Stefan}, biburl = {https://puma.ub.uni-stuttgart.de/bibtex/23ab43b2fd0e3bab4f1ce329e0ca15022/ajeltsch}, booktitle = {Chromatin Readers in Health and Disease}, doi = {https://doi.org/10.1016/B978-0-12-823376-4.00002-1}, editor = {Binda, Olivier}, interhash = {2598741d79f59477f2972fd07e00552c}, intrahash = {3ab43b2fd0e3bab4f1ce329e0ca15022}, isbn = {978-0-12-823376-4}, keywords = {}, pages = {3-11}, publisher = {Academic Press}, series = {Translational Epigenetics}, timestamp = {2024-01-13T10:21:22.000+0100}, title = {Chapter 1 - ADD domains—A regulatory hub in chromatin biology and disease}, url = {https://www.sciencedirect.com/science/article/pii/B9780128233764000021}, volume = 35, year = 2024 }