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A reconfigured pattern of MLL occupancy within mitotic chromatin promotes rapid transcriptional reactivation following mitotic exit.

Molecular cell | Dec 25, 2009

Mixed lineage leukemia (MLL) and its metazoan Trithorax orthologs have been linked with the epigenetic maintenance of transcriptional activity. To identify mechanisms by which MLL perpetuates active transcription in dividing cells, we investigated its role during M phase of the cell cycle. Unlike other chromatin-modifying enzymes examined, we found that MLL associates with gene promoters packaged within condensed mitotic chromosomes. Genome-wide location analysis identified a globally rearranged pattern of MLL occupancy during mitosis in a manner favoring genes that were highly transcribed during interphase. Knockdown experiments revealed that MLL retention at gene promoters during mitosis accelerates transcription reactivation following mitotic exit. MLL tethers Menin, RbBP5, and ASH2L to its occupied sites during mitosis, but is dispensable for preserving histone H3K4 methylation. These findings implicate mitotic bookmarking as a component of Trithorax-based gene regulation, which may facilitate inheritance of active gene expression states during cell division.

Pubmed ID: 20064463 RIS Download

Mesh terms: Animals | Chromatin | DNA-Binding Proteins | Gene Expression Regulation | HeLa Cells | Histone-Lysine N-Methyltransferase | Homeodomain Proteins | Humans | Interphase | Mitosis | Myeloid-Lymphoid Leukemia Protein | Neoplasm Proteins | Nuclear Proteins | Promoter Regions, Genetic | Proto-Oncogene Proteins | RNA Interference | RNA Polymerase II | Transcription Factors | Transcriptional Activation

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Associated grants

  • Agency: NIDDK NIH HHS, Id: R01 DK058044
  • Agency: NIDDK NIH HHS, Id: DK58044
  • Agency: NIDDK NIH HHS, Id: R01 DK058044-08
  • Agency: NHLBI NIH HHS, Id: T32 HL007150
  • Agency: NCI NIH HHS, Id: P30 CA01520
  • Agency: NIDDK NIH HHS, Id: R37 DK058044
  • Agency: NIDDK NIH HHS, Id: R01 DK054937
  • Agency: NIDDK NIH HHS, Id: DK54937
  • Agency: NIDDK NIH HHS, Id: R01 DK054937-11

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