TAILIEUCHUNG - Báo cáo khoa học: Dynamic association of MLL1, H3K4 trimethylation with chromatin and Hox gene expression during the cell cycle

Mixed lineage leukemias (MLLs) are histone H3 at lysine 4 (H3K4)-spe-cific methylases that play a critical role in regulating gene expression in humans. As chromatin condensation, relaxation and differential gene expression are keys to correct cell cycle progression, we analyzed the dynamic association of MLL and H3K4 trimethylation at different stages of the cell cycle. | ỊFEBS Journal Dynamic association of MLL1 H3K4 trimethylation with chromatin and Hox gene expression during the cell cycle Bibhu P. Mishra Khairul I. Ansari and Subhrangsu S. Mandal Department of Chemistry and Biochemistry The University of Texas at Arlington Arlington TX USA Keywords cell cycle H3K4 methylation histone methyltransferase Hox genes mixed lineage leukemia Correspondence S. S. Mandal Department of Chemistry and Biochemistry The University of Texas at Arlington Arlington TX 76019 USA Fax 1 817 272 3808 Tel 1 817 272 3804 E-mail smandal@ Received 6 November 2008 revised 3 January 2009 accepted 9 January 2009 doi Mixed lineage leukemias MLLs are histone H3 at lysine 4 H3K4 -spe-cific methylases that play a critical role in regulating gene expression in humans. As chromatin condensation relaxation and differential gene expression are keys to correct cell cycle progression we analyzed the dynamic association of MLL and H3K4 trimethylation at different stages of the cell cycle. Interestingly MLL1 which is normally associated with transcriptionally active chromatins G1 phase dissociates from condensed mitotic chromatin and returns at the end of telophase when the nucleus starts to relax. In contrast H3K4 trimethylation mark which is also normally associated with euchromatins in G1 remains associated even with condensed chromatin throughout the cell cycle. The global levels of MLL1 and H3K4 trimethylation are not affected during the cell cycle and H3Ser28 phosphorylation is only observed during mitosis. Interestingly MLL target homeobox-containing Hox genes HoxA5 HoxA7 and HoxA10 are differentially expressed during the cell cycle and the recruitment of MLL1 and H3K4 trimethylation levels are modulated in the promoter of these Hox genes as a function of their expression. In addition down-regulation of MLL1 results in cell cycle arrest at the G2 M phase. The fluctuation of H3K4 trimethylation marks at specific promoters .

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