| Global identification of MLL2-targeted loci reveals MLL2's role in diverse signaling pathways. | |
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MedLine Citation:
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PMID: 23045699 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-10-08 |
Journal Detail:
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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:
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Created Date: 2012-10-24 Completed Date: 2013-01-07 Revised Date: 2013-04-23 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 17603-8 Citation Subset: IM |
Affiliation:
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The Preston Robert Tisch Brain Tumor Center at Duke, Pediatric Brain Tumor Foundation Institute, cDepartment of Pathology, Duke University, Durham, NC 27710, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line, Tumor DNA-Binding Proteins / genetics, metabolism, physiology* Gene Knockdown Techniques Humans Neoplasm Proteins / genetics, metabolism, physiology* Protein Binding S100 Proteins / genetics Signal Transduction / physiology* Suppressor of Cytokine Signaling Proteins / genetics |
| Chemical | |
Reg. No./Substance:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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