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PMID: 20064463 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Molecular cell ·Vol. 36 ·No. 6 ·2009-12-25 ·Pages 970-83

Blobel GA, Kadauke S, Wang E, Lau AW, Zuber J, Chou MM, Vakoc CR

Abstract

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.

MeSH Terms
Animals Chromatin/genetics,metabolism DNA-Binding Proteins/genetics,metabolism Gene Expression Regulation HeLa Cells Histone-Lysine N-Methyltransferase/genetics,metabolism Homeodomain Proteins/genetics,metabolism Humans Interphase/genetics Mitosis/physiology Myeloid-Lymphoid Leukemia Protein/genetics,metabolism Neoplasm Proteins/genetics,metabolism Nuclear Proteins/genetics,metabolism Promoter Regions, Genetic Proto-Oncogene Proteins/genetics,metabolism RNA Interference RNA Polymerase II/genetics,metabolism Transcription Factors/genetics,metabolism Transcriptional Activation
Chemicals
ASH2L protein, human Chromatin DNA-Binding Proteins Homeodomain Proteins KMT2D protein, human MEN1 protein, human Neoplasm Proteins Nuclear Proteins Proto-Oncogene Proteins RBBP5 protein, human Transcription Factors Myeloid-Lymphoid Leukemia Protein Histone-Lysine N-Methyltransferase Setd1A protein, human RNA Polymerase II
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Blobel Gerd A
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Kadauke Stephan
Wang Eric
Lau Alan W
Zuber Johannes
Chou Margaret M
Vakoc Christopher R
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2009.12.001
Published
2009-12-25
Pages
970-83
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC2818742
Subset
IM
Grants
NIDDK NIH HHS · R01 DK058044 · United States
NIDDK NIH HHS · DK58044 · United States
NIDDK NIH HHS · R01 DK058044-08 · United States
NHLBI NIH HHS · T32 HL007150 · United States
NCI NIH HHS · P30 CA01520 · United States
NIDDK NIH HHS · R37 DK058044 · United States
NIDDK NIH HHS · R01 DK054937 · United States
NIDDK NIH HHS · DK54937 · United States
NIDDK NIH HHS · R01 DK054937-11 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2009.12.001 PMC Full Text View journal details
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