The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Export

@article{citeulike:3832916, abstract = {Histone methylation and DNA methylation cooperatively regulate chromatin structure and gene activity. How these two systems coordinate with each other remains unclear. Here we study the biological function of lysine-specific demethylase 1 (LSD1, also known as KDM1 and AOF2), which has been shown to demethylate histone H3 on lysine 4 (H3K4) and lysine 9 (H3K9). We show that LSD1 is required for gastrulation during mouse embryogenesis. Notably, targeted deletion of the gene encoding LSD1 (namely, Aof2) in embryonic stem (ES) cells induces progressive loss of DNA methylation. This loss correlates with a decrease in DNA methyltransferase 1 (Dnmt1) protein, as a result of reduced Dnmt1 stability. Dnmt1 protein is methylated in vivo, and its methylation is enhanced in the absence of LSD1. Furthermore, Dnmt1 can be methylated by Set7/9 (also known as KMT7) and demethylated by LSD1 in vitro. Our findings suggest that LSD1 demethylates and stabilizes Dnmt1, thus providing a previously unknown mechanistic link between the histone and DNA methylation systems.}, author = {Wang, Jing and Hevi, Sarah and Kurash, Julia K. and Lei, Hong and Gay, Fr\'{e}d\'{e}rique and Bajko, Jeffrey and Su, Hui and Sun, Weitao and Chang, Hua and Xu, Guoliang and Gaudet, Fran\c{c}ois and Li, En and Chen, Taiping}, citeulike-article-id = {3832916}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/ng.268}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/ng.268}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19098913}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19098913}, day = {21}, doi = {10.1038/ng.268}, issn = {1546-1718}, journal = {Nature genetics}, keywords = {epigenetics, epigenome, methylation, methylome}, month = {January}, number = {1}, pages = {125--129}, posted-at = {2009-01-09 12:08:31}, priority = {5}, publisher = {Nature Publishing Group}, title = {The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation.}, url = {http://dx.doi.org/10.1038/ng.268}, volume = {41}, year = {2009} }

TY - JOUR ID - citeulike:3832916 L3 - citeulike-article-id:3832916 N2 - Histone methylation and DNA methylation cooperatively regulate chromatin structure and gene activity. How these two systems coordinate with each other remains unclear. Here we study the biological function of lysine-specific demethylase 1 (LSD1, also known as KDM1 and AOF2), which has been shown to demethylate histone H3 on lysine 4 (H3K4) and lysine 9 (H3K9). We show that LSD1 is required for gastrulation during mouse embryogenesis. Notably, targeted deletion of the gene encoding LSD1 (namely, Aof2) in embryonic stem (ES) cells induces progressive loss of DNA methylation. This loss correlates with a decrease in DNA methyltransferase 1 (Dnmt1) protein, as a result of reduced Dnmt1 stability. Dnmt1 protein is methylated in vivo, and its methylation is enhanced in the absence of LSD1. Furthermore, Dnmt1 can be methylated by Set7/9 (also known as KMT7) and demethylated by LSD1 in vitro. Our findings suggest that LSD1 demethylates and stabilizes Dnmt1, thus providing a previously unknown mechanistic link between the histone and DNA methylation systems. IS - 1 JF - Nature genetics SN - 1546-1718 EP - 129 TI - The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. PB - Nature Publishing Group VL - 41 SP - 125 KW - epigenetics KW - epigenome KW - methylation KW - methylome AU - Wang, Jing AU - Hevi, Sarah AU - Kurash, Julia AU - Lei, Hong AU - Gay, Frédérique AU - Bajko, Jeffrey AU - Su, Hui AU - Sun, Weitao AU - Chang, Hua AU - Xu, Guoliang AU - Gaudet, François AU - Li, En AU - Chen, Taiping PY - 2009/01/21/ UR - http://dx.doi.org/10.1038/ng.268 ER -