Distribution of menin-occupied regions in chromatin specifies a broad role of menin in transcriptional regulation.
Menin is the protein product of the MEN1 tumor-suppressor gene; one allele of MEN1 is inactivated in the germ line of patients with "multiple endocrine neoplasia type 1" (MEN1) cancer syndrome. Menin interacts with several proteins involved in transcriptional regulation. RNA expression analyses have identified several menin-regulated genes that could represent proximal or distal interaction sites for menin. This report presents a substantial and unbiased sampling of menin-occupied chromatin regions using Serial Analysis of Chromatin Occupancy; this method combines chromatin immuno-precipitation with Serial Analysis of Gene Expression. Hundreds of menin-occupied genomic sites were identified in promoter regions (32% of menin-occupied loci), near the 3' end of genes (14%), or inside genes (21%), extending other data about menin recruitments to many sites of transcriptional activity. A large number of menin-occupied sites (33%) were located outside known gene regions. Additional annotation of the human genome could help in identifying genes at these loci, or these might be gene-free regions of the genome where menin occupancy could play some structural or regulatory role. Menin occupancy at many intragenic positions distant from the core promoter reveals an unexpected type of menin target region at many loci in the genome. These unbiased data also suggest that menin could play a broad role in transcriptional regulation.
Agarwal
Sunita K
SK
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1802, USA. sunitaa@mail.nih.gov
Impey
Soren
S
McWeeney
Shannon
S
Scacheri
Peter C
PC
Collins
Francis S
FS
Goodman
Richard H
RH
Spiegel
Allen M
AM
Marx
Stephen J
SJ
D020413:3' Untranslated Regions / Q000737:chemistry / Q000235:genetics; D020121:5' Untranslated Regions / Q000737:chemistry / Q000235:genetics; D002843:Chromatin / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology*
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D002843:Chromatin; C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D004247:DNA