Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis.

Peter C. Scacheri, Sean Davis, Duncan T. Odom, Gregory E. Crawford, Stacie Perkins, Mohamad J. Halawi, Sunita K. Agarwal, Stephen J. Marx, Allen M. Spiegel, Paul S. Meltzer, Francis S. Collins

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

Multiple endocrine neoplasia type I (MEN1) is a familial cancer syndrome characterized primarily by tumors of multiple endocrine glands. The gene for MEN1 encodes a ubiquitously expressed tumor suppressor protein called menin. Menin was recently shown to interact with several components of a trithorax family histone methyltransferase complex including ASH2, Rbbp5, WDR5, and the leukemia proto-oncoprotein MLL. To elucidate menin's role as a tumor suppressor and gain insights into the endocrine-specific tumor phenotype in MEN1, we mapped the genomic binding sites of menin, MLL1, and Rbbp5, to approximately 20,000 promoters in HeLa S3, HepG2, and pancreatic islet cells using the strategy of chromatin-immunoprecipitation coupled with microarray analysis. We found that menin, MLL1, and Rbbp5 localize to the promoters of thousands of human genes but do not always bind together. These data suggest that menin functions as a general regulator of transcription. We also found that factor occupancy generally correlates with high gene expression but that the loss of menin does not result in significant changes in most transcript levels. One exception is the developmentally programmed transcription factor, HLXB9, which is overexpressed in islets in the absence of menin. Our findings expand the realm of menin-targeted genes several hundred-fold beyond that previously described and provide potential insights to the endocrine tumor bias observed in MEN1 patients.

Original languageEnglish (US)
JournalPLoS Genetics
Volume2
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

Fingerprint

Multiple Endocrine Neoplasia Type 1
tumor
carcinogenesis
Carcinogenesis
genome
Genome
neoplasms
Neoplasms
Islets of Langerhans
islets of Langerhans
gene
Genes
Endocrine Glands
Tumor Suppressor Proteins
transcription factors
promoter regions
endocrine glands
Chromatin Immunoprecipitation
Oncogene Proteins
Microarray Analysis

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Scacheri, P. C., Davis, S., Odom, D. T., Crawford, G. E., Perkins, S., Halawi, M. J., ... Collins, F. S. (2006). Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis. PLoS Genetics, 2(4). https://doi.org/10.1371/journal.pgen.0020051

Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis. / Scacheri, Peter C.; Davis, Sean; Odom, Duncan T.; Crawford, Gregory E.; Perkins, Stacie; Halawi, Mohamad J.; Agarwal, Sunita K.; Marx, Stephen J.; Spiegel, Allen M.; Meltzer, Paul S.; Collins, Francis S.

In: PLoS Genetics, Vol. 2, No. 4, 04.2006.

Research output: Contribution to journalArticle

Scacheri, PC, Davis, S, Odom, DT, Crawford, GE, Perkins, S, Halawi, MJ, Agarwal, SK, Marx, SJ, Spiegel, AM, Meltzer, PS & Collins, FS 2006, 'Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis.', PLoS Genetics, vol. 2, no. 4. https://doi.org/10.1371/journal.pgen.0020051
Scacheri, Peter C. ; Davis, Sean ; Odom, Duncan T. ; Crawford, Gregory E. ; Perkins, Stacie ; Halawi, Mohamad J. ; Agarwal, Sunita K. ; Marx, Stephen J. ; Spiegel, Allen M. ; Meltzer, Paul S. ; Collins, Francis S. / Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis. In: PLoS Genetics. 2006 ; Vol. 2, No. 4.
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