PMID- 25537453
OWN - NLM
STAT- MEDLINE
DCOM- 20160204
LR  - 20201218
IS  - 1557-3125 (Electronic)
IS  - 1541-7786 (Linking)
VI  - 13
IP  - 4
DP  - 2015 Apr
TI  - Dynamic epigenetic regulation by menin during pancreatic islet tumor formation.
PG  - 689-98
LID - 10.1158/1541-7786.MCR-14-0457 [doi]
AB  - The tumor suppressor gene MEN1 is frequently mutated in sporadic pancreatic 
      neuroendocrine tumors (PanNET) and is responsible for the familial multiple 
      endocrine neoplasia type 1 (MEN-1) cancer syndrome. Menin, the protein product of 
      MEN1, associates with the histone methyltransferases (HMT) MLL1 (KMT2A) and MLL4 
      (KMT2B) to form menin-HMT complexes in both human and mouse model systems. To 
      elucidate the role of methylation of histone H3 at lysine 4 (H3K4) mediated by 
      menin-HMT complexes during PanNET formation, genome-wide histone H3 lysine 4 
      trimethylation (H3K4me3) signals were mapped in pancreatic islets using unbiased 
      chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq). 
      Integrative analysis of gene expression profiles and histone H3K4me3 levels 
      identified a number of transcripts and target genes dependent on menin. In the 
      absence of Men1, histone H3K27me3 levels are enriched, with a concomitant 
      decrease in H3K4me3 within the promoters of these target genes. In particular, 
      expression of the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) 
      gene is subject to dynamic epigenetic regulation by Men1-dependent histone 
      modification in a time-dependent manner. Decreased expression of IGF2BP2 in 
      Men1-deficient hyperplastic pancreatic islets is partially reversed by ablation 
      of RBP2 (KDM5A), a histone H3K4-specific demethylase of the jumonji, AT-rich 
      interactive domain 1 (JARID1) family. Taken together, these data demonstrate that 
      loss of Men1 in pancreatic islet cells alters the epigenetic landscape of its 
      target genes. IMPLICATIONS: Epigenetic profiling and gene expression analysis in 
      Men1-deficient pancreatic islet cells reveals vital insight into the molecular 
      events that occur during the progression of pancreatic islet tumorigenesis.
CI  - (c)2014 American Association for Cancer Research.
FAU - Lin, Wenchu
AU  - Lin W
AD  - Department of Medical Oncology, Center for Cancer Genome Discovery, Dana-Farber 
      Cancer Institute, Boston, Massachusetts. Department of Pathology, Brigham and 
      Women's Hospital and Harvard Medical School, Boston, Massachusetts. Cancer 
      program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts. High 
      Magnetic Field Laboratory, Chinese Academy of Sciences, 350 Shushanhu RD, Hefei, 
      Anhui Province, 230031, P. R. China.
FAU - Watanabe, Hideo
AU  - Watanabe H
AD  - Department of Medical Oncology, Center for Cancer Genome Discovery, Dana-Farber 
      Cancer Institute, Boston, Massachusetts. Department of Pathology, Brigham and 
      Women's Hospital and Harvard Medical School, Boston, Massachusetts. Cancer 
      program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
FAU - Peng, Shouyong
AU  - Peng S
AD  - Department of Medical Oncology, Center for Cancer Genome Discovery, Dana-Farber 
      Cancer Institute, Boston, Massachusetts. Department of Pathology, Brigham and 
      Women's Hospital and Harvard Medical School, Boston, Massachusetts. Cancer 
      program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
FAU - Francis, Joshua M
AU  - Francis JM
AD  - Department of Medical Oncology, Center for Cancer Genome Discovery, Dana-Farber 
      Cancer Institute, Boston, Massachusetts. Department of Pathology, Brigham and 
      Women's Hospital and Harvard Medical School, Boston, Massachusetts. Cancer 
      program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
FAU - Kaplan, Nathan
AU  - Kaplan N
AD  - Department of Medical Oncology, Center for Cancer Genome Discovery, Dana-Farber 
      Cancer Institute, Boston, Massachusetts. Department of Pathology, Brigham and 
      Women's Hospital and Harvard Medical School, Boston, Massachusetts. Cancer 
      program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
FAU - Pedamallu, Chandra Sekhar
AU  - Pedamallu CS
AD  - Department of Medical Oncology, Center for Cancer Genome Discovery, Dana-Farber 
      Cancer Institute, Boston, Massachusetts. Department of Pathology, Brigham and 
      Women's Hospital and Harvard Medical School, Boston, Massachusetts. Cancer 
      program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
FAU - Ramachandran, Aruna
AU  - Ramachandran A
AD  - Department of Medical Oncology, Center for Cancer Genome Discovery, Dana-Farber 
      Cancer Institute, Boston, Massachusetts. Department of Pathology, Brigham and 
      Women's Hospital and Harvard Medical School, Boston, Massachusetts. Cancer 
      program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
FAU - Agoston, Agoston
AU  - Agoston A
AD  - Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, Massachusetts.
FAU - Bass, Adam J
AU  - Bass AJ
AD  - Department of Medical Oncology, Center for Cancer Genome Discovery, Dana-Farber 
      Cancer Institute, Boston, Massachusetts. Department of Pathology, Brigham and 
      Women's Hospital and Harvard Medical School, Boston, Massachusetts. Cancer 
      program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
FAU - Meyerson, Matthew
AU  - Meyerson M
AD  - Department of Medical Oncology, Center for Cancer Genome Discovery, Dana-Farber 
      Cancer Institute, Boston, Massachusetts. Department of Pathology, Brigham and 
      Women's Hospital and Harvard Medical School, Boston, Massachusetts. Cancer 
      program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts. 
      matthew_meyerson@dfci.harvard.edu.
LA  - eng
PT  - Journal Article
DEP - 20141223
PL  - United States
TA  - Mol Cancer Res
JT  - Molecular cancer research : MCR
JID - 101150042
RN  - 0 (Histones)
RN  - 0 (IGF2BP2 protein, mouse)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA-Binding Proteins)
SB  - IM
MH  - Adenoma, Islet Cell
MH  - Animals
MH  - *Epigenesis, Genetic
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Histones/metabolism
MH  - Humans
MH  - Methylation
MH  - Mice
MH  - Molecular Sequence Data
MH  - Neuroendocrine Tumors/*genetics/*pathology
MH  - Proto-Oncogene Proteins/*genetics
MH  - RNA-Binding Proteins/*genetics
EDAT- 2014/12/30 06:00
MHDA- 2016/02/05 06:00
CRDT- 2014/12/25 06:00
PHST- 2014/08/18 00:00 [received]
PHST- 2014/11/26 00:00 [accepted]
PHST- 2014/12/25 06:00 [entrez]
PHST- 2014/12/30 06:00 [pubmed]
PHST- 2016/02/05 06:00 [medline]
AID - 1541-7786.MCR-14-0457 [pii]
AID - 10.1158/1541-7786.MCR-14-0457 [doi]
PST - ppublish
SO  - Mol Cancer Res. 2015 Apr;13(4):689-98. doi: 10.1158/1541-7786.MCR-14-0457. Epub 
      2014 Dec 23.