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 Hess, Matthew Meyerson

Research output: Contribution to journalArticle

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Abstract

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
Volume13
Issue number4
DOIs
StatePublished - Feb 27 2004
Externally publishedYes

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Multiple Endocrine Neoplasia Type 1
Histone Code
Tumor Suppressor Proteins
Homeobox Genes
Chromatin Immunoprecipitation
Histones
Genes
Lysine
Neoplasms
Embryonic Structures
Yeasts
histone methyltransferase
Proteins

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Hughes, C. M., Rozenblatt-Rosen, O., Milne, T. A., Copeland, T. D., Levine, S. S., Lee, J. C., ... Meyerson, M. (2004). Menin associates with a trithorax family histone methyltransferase complex and with the Hoxc8 locus. Molecular Cell, 13(4), 587-597. https://doi.org/10.1016/S1097-2765(04)00081-4

Menin associates with a trithorax family histone methyltransferase complex and with the Hoxc8 locus. / Hughes, Christina M.; Rozenblatt-Rosen, Orit; Milne, Thomas A.; Copeland, Terry D.; Levine, Stuart S.; Lee, Jeffrey C.; Hayes, D. Neil; Shanmugam, Kalai Selvi; Bhattacharjee, Arindam; Biondi, Christine A.; Kay, Graham F.; Hayward, Nicholas K.; Hess, Jay; Meyerson, Matthew.

In: Molecular Cell, Vol. 13, No. 4, 27.02.2004, p. 587-597.

Research output: Contribution to journalArticle

Hughes, CM, Rozenblatt-Rosen, O, Milne, TA, Copeland, TD, Levine, SS, Lee, JC, Hayes, DN, Shanmugam, KS, Bhattacharjee, A, Biondi, CA, Kay, GF, Hayward, NK, Hess, J & Meyerson, M 2004, 'Menin associates with a trithorax family histone methyltransferase complex and with the Hoxc8 locus', Molecular Cell, vol. 13, no. 4, pp. 587-597. https://doi.org/10.1016/S1097-2765(04)00081-4
Hughes CM, Rozenblatt-Rosen O, Milne TA, Copeland TD, Levine SS, Lee JC et al. Menin associates with a trithorax family histone methyltransferase complex and with the Hoxc8 locus. Molecular Cell. 2004 Feb 27;13(4):587-597. https://doi.org/10.1016/S1097-2765(04)00081-4
Hughes, Christina M. ; Rozenblatt-Rosen, Orit ; Milne, Thomas A. ; Copeland, Terry D. ; Levine, Stuart S. ; Lee, Jeffrey C. ; Hayes, D. Neil ; Shanmugam, Kalai Selvi ; Bhattacharjee, Arindam ; Biondi, Christine A. ; Kay, Graham F. ; Hayward, Nicholas K. ; Hess, Jay ; Meyerson, Matthew. / Menin associates with a trithorax family histone methyltransferase complex and with the Hoxc8 locus. In: Molecular Cell. 2004 ; Vol. 13, No. 4. pp. 587-597.
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