PMID- 22666422
OWN - NLM
STAT- MEDLINE
DCOM- 20121029
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 5
DP  - 2012
TI  - Genome-wide characterization of menin-dependent H3K4me3 reveals a specific role 
      for menin in the regulation of genes implicated in MEN1-like tumors.
PG  - e37952
LID - 10.1371/journal.pone.0037952 [doi]
LID - e37952
AB  - Inactivating mutations in the MEN1 gene predisposing to the multiple endocrine 
      neoplasia type 1 (MEN1) syndrome can also cause sporadic pancreatic endocrine 
      tumors. MEN1 encodes menin, a subunit of MLL1/MLL2-containing histone 
      methyltransferase complexes that trimethylate histone H3 at lysine 4 (H3K4me3). 
      The importance of menin-dependent H3K4me3 in normal and transformed pancreatic 
      endocrine cells is unclear. To study the role of menin-dependent H3K4me3, we 
      performed in vitro differentiation of wild-type as well as menin-null mouse 
      embryonic stem cells (mESCs) into pancreatic islet-like endocrine cells (PILECs). 
      Gene expression analysis and genome-wide H3K4me3 ChIP-Seq profiling in wild-type 
      and menin-null mESCs and PILECs revealed menin-dependent H3K4me3 at the imprinted 
      Dlk1-Meg3 locus in mESCs, and all four Hox loci in differentiated PILECs. 
      Specific and significant loss of H3K4me3 and gene expression was observed for 
      genes within the imprinted Dlk1-Meg3 locus in menin-null mESCs and the Hox loci 
      in menin-null PILECs. Given that the reduced expression of genes within the 
      DLK1-MEG3 locus and the HOX loci is associated with MEN1-like sporadic tumors, 
      our data suggests a possible role for menin-dependent H3K4me3 at these genes in 
      the initiation and progression of sporadic pancreatic endocrine tumors. 
      Furthermore, our investigation also demonstrates that menin-null mESCs can be 
      differentiated in vitro into islet-like endocrine cells, underscoring the utility 
      of menin-null mESC-derived specialized cell types for genome-wide high-throughput 
      studies.
FAU - Agarwal, Sunita K
AU  - Agarwal SK
AD  - Metabolic Diseases Branch, National Institute of Diabetes and Digestive and 
      Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States 
      of America. SunitaA@mail.nih.gov
FAU - Jothi, Raja
AU  - Jothi R
LA  - eng
SI  - GEO/GSE37776
GR  - ZIA DK075035/Intramural NIH HHS/United States
GR  - ZIA ES102625/Intramural NIH HHS/United States
GR  - 1ZIADK075035-03/PHS HHS/United States
GR  - 1ZIAES102625-03/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120530
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Histones)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Embryonic Stem Cells/cytology/metabolism
MH  - Endocrine Cells/cytology/metabolism
MH  - Gene Deletion
MH  - *Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Genes, Homeobox/genetics
MH  - Genetic Loci/genetics
MH  - *Genomics
MH  - Histones/*chemistry/*metabolism
MH  - Humans
MH  - Islets of Langerhans/cytology
MH  - Methylation
MH  - Mice
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/metabolism
MH  - Pancreatic Neoplasms/genetics/metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Proto-Oncogene Proteins/deficiency/genetics/*metabolism
PMC - PMC3364203
COIS- Competing Interests: The authors have declared that co-author Raja Jothi is a 
      PLoS ONE Editorial Board member, and that this does not alter the authors' 
      adherence to all the PLoS ONE policies on sharing data and materials.
EDAT- 2012/06/06 06:00
MHDA- 2012/10/30 06:00
PMCR- 2012/05/30
CRDT- 2012/06/06 06:00
PHST- 2012/02/09 00:00 [received]
PHST- 2012/04/30 00:00 [accepted]
PHST- 2012/06/06 06:00 [entrez]
PHST- 2012/06/06 06:00 [pubmed]
PHST- 2012/10/30 06:00 [medline]
PHST- 2012/05/30 00:00 [pmc-release]
AID - PONE-D-12-04364 [pii]
AID - 10.1371/journal.pone.0037952 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(5):e37952. doi: 10.1371/journal.pone.0037952. Epub 2012 May 30.