MLL targets SET domain methyltransferase activity to Hox gene promoters

Thomas A. Milne, Scott D. Briggs, Hugh W. Brock, Mary Ellen Martin, Denise Gibbs, C. David Allis, Jay Hess

Research output: Contribution to journalArticle

754 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1107-1117
Number of pages11
JournalMolecular Cell
Volume10
Issue number5
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

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Homeobox Genes
Methyltransferases
Gene Expression
Histones
Methylation
Mammalian Embryo
Proteins
Transcriptional Activation
Lysine
Drosophila
Leukemia
Peptides
Genes

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Milne, T. A., Briggs, S. D., Brock, H. W., Martin, M. E., Gibbs, D., Allis, C. D., & Hess, J. (2002). MLL targets SET domain methyltransferase activity to Hox gene promoters. Molecular Cell, 10(5), 1107-1117. https://doi.org/10.1016/S1097-2765(02)00741-4

MLL targets SET domain methyltransferase activity to Hox gene promoters. / Milne, Thomas A.; Briggs, Scott D.; Brock, Hugh W.; Martin, Mary Ellen; Gibbs, Denise; Allis, C. David; Hess, Jay.

In: Molecular Cell, Vol. 10, No. 5, 01.11.2002, p. 1107-1117.

Research output: Contribution to journalArticle

Milne, TA, Briggs, SD, Brock, HW, Martin, ME, Gibbs, D, Allis, CD & Hess, J 2002, 'MLL targets SET domain methyltransferase activity to Hox gene promoters', Molecular Cell, vol. 10, no. 5, pp. 1107-1117. https://doi.org/10.1016/S1097-2765(02)00741-4
Milne TA, Briggs SD, Brock HW, Martin ME, Gibbs D, Allis CD et al. MLL targets SET domain methyltransferase activity to Hox gene promoters. Molecular Cell. 2002 Nov 1;10(5):1107-1117. https://doi.org/10.1016/S1097-2765(02)00741-4
Milne, Thomas A. ; Briggs, Scott D. ; Brock, Hugh W. ; Martin, Mary Ellen ; Gibbs, Denise ; Allis, C. David ; Hess, Jay. / MLL targets SET domain methyltransferase activity to Hox gene promoters. In: Molecular Cell. 2002 ; Vol. 10, No. 5. pp. 1107-1117.
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