Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2009-6-3
pubmed:abstractText
Mixed lineage leukemias (MLLs) are histone-methylating enzymes with critical roles in gene expression, epigenetics and cancer. Although MLLs are important gene regulators little is known about their own regulation. Herein, to understand the effects of toxic stress on MLL gene regulation, we treated human cells with a common food contaminant mycotoxin, deoxynivalenol (DON). Our results demonstrate that MLLs and Hox genes are overexpressed upon exposure to DON. Studies using specific inhibitors demonstrated that Src kinase families are involved in upstream events in DON-mediated upregulation of MLL1. Sequence analysis demonstrated that the MLL1 promoter contains multiple Sp1-binding sites and importantly, the binding of Sp1 is enriched in the MLL1 promoter upon exposure to DON. Moreover, antisense-mediated knockdown of Sp1 diminished DON-induced MLL1 upregulation. These results demonstrated that MLL1 gene expression is sensitive to toxic stress and Sp1 plays crucial roles in the stress-induced upregulation of MLL1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1742-4658
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3299-307
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19438726-Binding Sites, pubmed-meshheading:19438726-Blotting, Western, pubmed-meshheading:19438726-Cell Line, Tumor, pubmed-meshheading:19438726-Chromatin Immunoprecipitation, pubmed-meshheading:19438726-Dose-Response Relationship, Drug, pubmed-meshheading:19438726-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19438726-Homeodomain Proteins, pubmed-meshheading:19438726-Humans, pubmed-meshheading:19438726-Myeloid-Lymphoid Leukemia Protein, pubmed-meshheading:19438726-Oligonucleotides, Antisense, pubmed-meshheading:19438726-Promoter Regions, Genetic, pubmed-meshheading:19438726-Protein Binding, pubmed-meshheading:19438726-Pyrimidines, pubmed-meshheading:19438726-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19438726-Sp2 Transcription Factor, pubmed-meshheading:19438726-Transfection, pubmed-meshheading:19438726-Trichothecenes, pubmed-meshheading:19438726-src-Family Kinases
pubmed:year
2009
pubmed:articleTitle
Overexpression of human histone methylase MLL1 upon exposure to a food contaminant mycotoxin, deoxynivalenol.
pubmed:affiliation
Department of Chemistry and Biochemistry, The University of Texas at Arlington, TX 76019, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't