Document Detail

Global identification of MLL2-targeted loci reveals MLL2's role in diverse signaling pathways.
MedLine Citation:
PMID:  23045699     Owner:  NLM     Status:  MEDLINE    
Myeloid/lymphoid or mixed-lineage leukemia (MLL)-family genes encode histone lysine methyltransferases that play important roles in epigenetic regulation of gene transcription. MLL genes are frequently mutated in human cancers. Unlike MLL1, MLL2 (also known as ALR/MLL4) and its homolog MLL3 are not well-understood. Specifically, little is known regarding the extent of global MLL2 involvement in the regulation of gene expression and the mechanism underlying its alterations in driving tumorigenesis. Here we profile the global loci targeted by MLL2. A combinatorial analysis of the MLL2 binding profile and gene expression in MLL2 wild-type versus MLL2-null isogenic cell lines identified direct transcriptional target genes and revealed the connection of MLL2 to multiple cellular signaling pathways, including the p53 pathway, cAMP-mediated signaling, and cholestasis signaling. In particular, we demonstrate that MLL2 participates in retinoic acid receptor signaling by promoting retinoic acid-responsive gene transcription. Our results present a genome-wide integrative analysis of the MLL2 target loci and suggest potential mechanisms underlying tumorigenesis driven by MLL2 alterations.
Changcun Guo; Chun-Chi Chang; Matthew Wortham; Lee H Chen; Dawn N Kernagis; Xiaoxia Qin; Young-Wook Cho; Jen-Tsan Chi; Gerald A Grant; Roger E McLendon; Hai Yan; Kai Ge; Nickolas Papadopoulos; Darell D Bigner; Yiping He
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-24     Completed Date:  2013-01-07     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17603-8     Citation Subset:  IM    
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MeSH Terms
Cell Line, Tumor
DNA-Binding Proteins / genetics,  metabolism,  physiology*
Gene Knockdown Techniques
Neoplasm Proteins / genetics,  metabolism,  physiology*
Protein Binding
S100 Proteins / genetics
Signal Transduction / physiology*
Suppressor of Cytokine Signaling Proteins / genetics
Grant Support
Reg. No./Substance:
0/ASB2 protein, human; 0/DNA-Binding Proteins; 0/MLL2 protein, human; 0/Neoplasm Proteins; 0/S100 Proteins; 0/S100A1 protein; 0/Suppressor of Cytokine Signaling Proteins

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