Document Detail

Selective di- or trimethylation of histone H3 lysine 76 by two DOT1 homologs is important for cell cycle regulation in Trypanosoma brucei.
MedLine Citation:
PMID:  16916638     Owner:  NLM     Status:  MEDLINE    
DOT1 is an evolutionarily conserved histone H3 lysine 79 (H3K79) methyltransferase. K79 methylation is associated with transcriptional activation, meiotic checkpoint control, and DNA double-strand break (DSB) responses. Trypanosoma brucei has two homologs, DOT1A and DOT1B, which are responsible for dimethylation and trimethylation of H3K76, respectively (K76 in T. brucei is synonymous to K79 in other organisms). K76 dimethylation is only detectable during mitosis, whereas trimethylation occurs throughout the cell cycle. Deletion of DOT1B resulted in dimethylation of K76 throughout the cell cycle and caused subtle defects in cell cycle regulation and impaired differentiation. RNAi-mediated depletion of DOT1A appears to disrupt a mitotic checkpoint, resulting in premature progression through mitosis without DNA replication, generating a high proportion of cells with a haploid DNA content, an unprecedented state for trypanosomes. We propose that DOT1A and DOT1B influence the trypanosome cell cycle by regulating the degree of H3K76 methylation.
Christian J Janzen; Sandra B Hake; Joanna E Lowell; George A M Cross
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular cell     Volume:  23     ISSN:  1097-2765     ISO Abbreviation:  Mol. Cell     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-18     Completed Date:  2006-09-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9802571     Medline TA:  Mol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  497-507     Citation Subset:  IM    
Laboratory of Molecular Parasitology, The Rockefeller University, New York, New York 10021, USA.
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MeSH Terms
5' Untranslated Regions / genetics
Amino Acid Sequence
Base Sequence
Cell Differentiation
Conserved Sequence / genetics
Gene Expression
Genes, Developmental
Histones / metabolism*
Life Cycle Stages
Lysine / metabolism*
Molecular Sequence Data
Nucleosomes / metabolism
Protozoan Proteins / chemistry,  genetics,  metabolism*
Sequence Alignment
Sequence Homology, Amino Acid*
Trypanosoma brucei brucei / cytology*,  growth & development
Grant Support
Reg. No./Substance:
0/5' Untranslated Regions; 0/Histones; 0/Nucleosomes; 0/Protozoan Proteins; 56-87-1/Lysine

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