PMID- 17356705 OWN - NLM STAT- MEDLINE DCOM- 20070412 LR - 20190608 IS - 1476-5586 (Electronic) IS - 1522-8002 (Print) IS - 1476-5586 (Linking) VI - 9 IP - 2 DP - 2007 Feb TI - Distribution of menin-occupied regions in chromatin specifies a broad role of menin in transcriptional regulation. PG - 101-7 AB - 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. FAU - Agarwal, Sunita K AU - Agarwal SK AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1802, USA. sunitaa@mail.nih.gov FAU - Impey, Soren AU - Impey S FAU - McWeeney, Shannon AU - McWeeney S FAU - Scacheri, Peter C AU - Scacheri PC FAU - Collins, Francis S AU - Collins FS FAU - Goodman, Richard H AU - Goodman RH FAU - Spiegel, Allen M AU - Spiegel AM FAU - Marx, Stephen J AU - Marx SJ LA - eng GR - R37 DK045423/DK/NIDDK NIH HHS/United States GR - DK45423/DK/NIDDK NIH HHS/United States GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PL - United States TA - Neoplasia JT - Neoplasia (New York, N.Y.) JID - 100886622 RN - 0 (3' Untranslated Regions) RN - 0 (5' Untranslated Regions) RN - 0 (Chromatin) RN - 0 (MEN1 protein, human) RN - 0 (Proto-Oncogene Proteins) RN - 9007-49-2 (DNA) SB - IM MH - 3' Untranslated Regions/chemistry/genetics MH - 5' Untranslated Regions/chemistry/genetics MH - Chromatin/*genetics MH - DNA/genetics/*metabolism MH - Gene Expression Profiling/*methods MH - Gene Expression Regulation/genetics/*physiology MH - Gene Library MH - HeLa Cells MH - Humans MH - Immunoprecipitation MH - Multiple Endocrine Neoplasia Type 1/genetics MH - Plasmids/genetics MH - Polymerase Chain Reaction MH - Promoter Regions, Genetic/*genetics MH - Protein Binding MH - Proto-Oncogene Proteins/analysis/*physiology MH - Transcription, Genetic/genetics/*physiology PMC - PMC1813935 EDAT- 2007/03/16 09:00 MHDA- 2007/04/14 09:00 PMCR- 2007/02/01 CRDT- 2007/03/16 09:00 PHST- 2006/11/03 00:00 [received] PHST- 2006/12/27 00:00 [revised] PHST- 2006/12/29 00:00 [accepted] PHST- 2007/03/16 09:00 [pubmed] PHST- 2007/04/14 09:00 [medline] PHST- 2007/03/16 09:00 [entrez] PHST- 2007/02/01 00:00 [pmc-release] AID - 06706 [pii] AID - 10.1593/neo.06706 [doi] PST - ppublish SO - Neoplasia. 2007 Feb;9(2):101-7. doi: 10.1593/neo.06706.