Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression

Yokoyama, A., Wang, Z., Wysocka, J., Sanyal, M., Aufiero, D. J., Kitabayashi, I., Herr, W., Cleary, M. L. (July 2004) Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression. Molecular and Cellular Biology, 24 (13). pp. 5639-5649. ISSN 0270-7306

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Abstract

MLL (for mixed-lineage leukemia) is a proto-oncogene that is mutated in a variety of human leukemias. Its product, a homolog of Drosophila melanogaster trithorax, displays intrinsic histone methyltransferase activity and functions genetically to maintain embryonic Hox gene expression. Here we report the biochemical purification of MLL and demonstrate that it associates with a cohort of proteins shared with the yeast and human SET1 histone methyltransferase complexes, including a homolog of Ash2, another Trx-G group protein. Two other members of the novel MLL complex identified here are host cell factor I (HCF-1), a transcriptional coregulator, and the related HCF-2, both of which specifically interact with a conserved binding motif in the MLLN (p300) subunit of MILL and provide a potential mechanism for regulating its antagonistic transcriptional properties. Menin, a product of the MEN1 tumor suppressor gene, is also a component of the 1-MDa MLL complex. Abrogation of menin expression phenocopies loss of MLL and reveals a critical role for menin in the maintenance of Hox gene expression. Oncogenic mutant forms of MLL retain an ability to interact with menin but not other identified complex components. These studies link the menin tumor suppressor protein with the MLL histone methyltransferase machinery, with implications for Hox gene expression in development and leukemia pathogenesis.

Item Type: Paper
Additional Information: ISI Document Delivery No.: 830UL
Uncontrolled Keywords: SET-DOMAIN set-domain TUMOR-SUPPRESSOR tumor suppressor HEMATOLOGICAL MALIGNANCIES hematological malignancies CHROMOSOMAL chromosomal TRANSLOCATIONS translocations TRANSCRIPTIONAL REGULATION transcriptional regulation SACCHAROMYCES-CEREVISIAE saccharomyces cereviciae DROSOPHILA-TRITHORAX Drosophila Trithorax PROTEOLYTIC CLEAVAGE proteolytic cleavage MAMMALIAN TRITHORAX mammalian trithorax REPRESSION DOMAIN repression domain
Subjects: biotechnology > chromatography
diseases & disorders > cancer > cancer types > leukemia
CSHL Authors:
Depositing User: CSHL Librarian
Date: July 2004
Date Deposited: 17 Jan 2012 19:32
Last Modified: 17 Jan 2012 19:32
URI: http://repository.cshl.edu/id/eprint/22519

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