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Overexpression of human histone methylase MLL 1 upon exposure to a food contaminant mycotoxin, deoxynivalenol
Author(s) -
Ansari Khairul I.,
Hussain Imran,
Das Hriday K.,
Mandal Subhrangsu S.
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07055.x
Subject(s) - downregulation and upregulation , biology , gene knockdown , histone methyltransferase , gene , protein arginine methyltransferase 5 , epigenetics , regulation of gene expression , histone , gene expression , methyltransferase , genetics , microbiology and biotechnology , methylation
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 MLL 1 promoter contains multiple Sp1‐binding sites and importantly, the binding of Sp 1 is enriched in the MLL 1 promoter upon exposure to DON. Moreover, antisense‐mediated knockdown of Sp 1 diminished DON‐induced MLL 1 upregulation. These results demonstrated that MLL 1 gene expression is sensitive to toxic stress and Sp 1 plays crucial roles in the stress‐induced upregulation of MLL1.