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Publication : MLL targets SET domain methyltransferase activity to Hox gene promoters.

First Author  Milne TA Year  2002
Journal  Mol Cell Volume  10
Issue  5 Pages  1107-17
PubMed ID  12453418 Mgi Jnum  J:80575
Mgi Id  MGI:2446369 Doi  10.1016/s1097-2765(02)00741-4
Citation  Milne TA, et al. (2002) MLL Targets SET Domain Methyltransferase Activity to Hox Gene Promoters. Mol Cell 10(5):1107-17
abstractText  MLL, the human homolog of Drosophila trithorax, maintains Hox gene expression in mammalian embryos and is rearranged in human leukemias resulting in Hox gene deregulation. How MLL or MLL fusion proteins regulate gene expression remains obscure. We show that MLL regulates target Hox gene expression through direct binding to promoter sequences. We further show that the MLL SET domain is a histone H3 lysine 4-specific methyltransferase whose activity is stimulated with acetylated H3 peptides. This methylase activity is associated with Hox gene activation and H3 (Lys4) methylation at cis-regulatory sequences in vivo. A leukemogenic MLL fusion protein that activates Hox expression had no effect on histone methylation, suggesting a distinct mechanism for gene regulation by MLL and MLL fusion proteins.
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