Menin associates with a trithorax family histone methyltransferase complex and with the Hoxc8 locus

Christina M. Hughes, Orit Rozenblatt-Rosen, Thomas A. Milne, Terry D. Copeland, Stuart S. Levine, Jeffrey C. Lee, D. Neil Hayes, Kalai Selvi Shanmugam, Arindam Bhattacharjee, Christine A. Biondi, Graham F. Kay, Nicholas K. Hayward, Jay L. Hess, Matthew Meyerson

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431 Scopus citations


The cellular function of the menin tumor suppressor protein, product of the MEN1 gene mutated in familial multiple endocrine neoplasia type 1, has not been defined. We now show that menin is associated with a histone methyltransferase complex containing two trithorax family proteins, MLL2 and Ash2L, and other homologs of the yeast Set1 assembly. This menin-associated complex methylates histone H3 on lysine 4. A subset of tumor-derived menin mutants lacks the associated histone methyltransferase activity. In addition, menin is associated with RNA polymerase II whose large subunit carboxyl-terminal domain is phosphorylated on Ser 5. Men1 knockout embryos and cells show decreased expression of the homeobox genes Hoxc6 and Hoxc8. Chromatin immunoprecipitation experiments reveal that menin is bound to the Hoxc8 locus. These results suggest that menin activates the transcription of differentiation-regulating genes by covalent histone modification, and that this activity is related to tumor suppression by MEN1.

Original languageEnglish (US)
Pages (from-to)587-597
Number of pages11
JournalMolecular Cell
Issue number4
StatePublished - Feb 27 2004


ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Hughes, C. M., Rozenblatt-Rosen, O., Milne, T. A., Copeland, T. D., Levine, S. S., Lee, J. C., Hayes, D. N., Shanmugam, K. S., Bhattacharjee, A., Biondi, C. A., Kay, G. F., Hayward, N. K., Hess, J. L., & Meyerson, M. (2004). Menin associates with a trithorax family histone methyltransferase complex and with the Hoxc8 locus. Molecular Cell, 13(4), 587-597.