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

Publication ,  Journal Article
Scacheri, PC; Davis, S; Odom, DT; Crawford, GE; Perkins, S; Halawi, MJ; Agarwal, SK; Marx, SJ; Spiegel, AM; Meltzer, PS; Collins, FS
Published in: PLoS Genet
April 2006

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.

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Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

April 2006

Volume

2

Issue

4

Start / End Page

e51

Location

United States

Related Subject Headings

  • Transcription Factors
  • Proto-Oncogene Proteins
  • Protein Binding
  • Promoter Regions, Genetic
  • Phenotype
  • Oligonucleotide Array Sequence Analysis
  • Nuclear Proteins
  • Myeloid-Lymphoid Leukemia Protein
  • Models, Genetic
  • Humans
 

Citation

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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 Genet, 2(4), e51. https://doi.org/10.1371/journal.pgen.0020051
Scacheri, Peter C., Sean Davis, Duncan T. Odom, Gregory E. Crawford, Stacie Perkins, Mohamad J. Halawi, Sunita K. Agarwal, et al. “Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis.PLoS Genet 2, no. 4 (April 2006): e51. https://doi.org/10.1371/journal.pgen.0020051.
Scacheri PC, Davis S, Odom DT, Crawford GE, Perkins S, Halawi MJ, et al. Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis. PLoS Genet. 2006 Apr;2(4):e51.
Scacheri, Peter C., et al. “Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis.PLoS Genet, vol. 2, no. 4, Apr. 2006, p. e51. Pubmed, doi:10.1371/journal.pgen.0020051.
Scacheri PC, Davis S, Odom DT, Crawford GE, Perkins S, Halawi MJ, Agarwal SK, Marx SJ, Spiegel AM, Meltzer PS, Collins FS. Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis. PLoS Genet. 2006 Apr;2(4):e51.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

April 2006

Volume

2

Issue

4

Start / End Page

e51

Location

United States

Related Subject Headings

  • Transcription Factors
  • Proto-Oncogene Proteins
  • Protein Binding
  • Promoter Regions, Genetic
  • Phenotype
  • Oligonucleotide Array Sequence Analysis
  • Nuclear Proteins
  • Myeloid-Lymphoid Leukemia Protein
  • Models, Genetic
  • Humans