PMID- 23579270
OWN - NLM
STAT- MEDLINE
DCOM- 20130823
LR  - 20211021
IS  - 2041-4889 (Electronic)
VI  - 4
IP  - 4
DP  - 2013 Apr 11
TI  - Menin mediates epigenetic regulation via histone H3 lysine 9 methylation.
PG  - e583
LID - 10.1038/cddis.2013.98 [doi]
AB  - Menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is a tumor 
      suppressor that leads to multiple endocrine tumors upon loss of its function. 
      Menin functions as a transcriptional activator by tethering MLL complex to 
      mediate histone H3 K4 methylation. It also functions as a repressor. However, the 
      molecular mechanism of how menin contributes to the opposite outcome in gene 
      expression is largely unknown. Here, we investigated the role of menin in the 
      epigenetic regulation of transcription mediated by histone covalent modification. 
      We show that the global methylation level of histone H3 K9, as well as H3 K4, was 
      decreased in Men1(-/-) MEF cells. Consistently, menin was able to interact with 
      the suppressor of variegation 3-9 homolog family protein, SUV39H1, to mediate H3 
      K9 methylation. This interaction decreased when patient-derived MEN1 mutation was 
      introduced into the SUV39H1-interaction domain. We show that menin mediated 
      different chromatin changes depending on target genes. Chromatin 
      immunoprecipitation studies showed that menin directly associated with the GBX2 
      promoter and menin-dependent recruitment of SUV39H1 was essential for chromatin 
      remodeling and transcriptional regulation. These results provide a molecular 
      basis of how menin functions as a transcriptional repressor and suggest that 
      menin-dependent integration of H3 K9 methylation might play an important role in 
      preventing tumors.
FAU - Yang, Y-J
AU  - Yang YJ
AD  - School of Pharmacy, Sungkyunkwan University, Jangan-gu, Suwon, Republic of Korea.
FAU - Song, T-Y
AU  - Song TY
FAU - Park, J
AU  - Park J
FAU - Lee, J
AU  - Lee J
FAU - Lim, J
AU  - Lim J
FAU - Jang, H
AU  - Jang H
FAU - Kim, Y-N
AU  - Kim YN
FAU - Yang, J-H
AU  - Yang JH
FAU - Song, Y
AU  - Song Y
FAU - Choi, A
AU  - Choi A
FAU - Lee, H Y
AU  - Lee HY
FAU - Jo, C H
AU  - Jo CH
FAU - Han, J W
AU  - Han JW
FAU - Kim, S-T
AU  - Kim ST
FAU - Youn, H-D
AU  - Youn HD
FAU - Cho, E-J
AU  - Cho EJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130411
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (GBX2 protein, human)
RN  - 0 (Histones)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Repressor Proteins)
RN  - EC 2.1.1. (SUV39H1 protein, human)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Animals
MH  - Cell Transformation, Neoplastic/genetics/*metabolism
MH  - *Chromatin Assembly and Disassembly
MH  - *Epigenesis, Genetic
MH  - Fibroblasts/metabolism/pathology
MH  - HEK293 Cells
MH  - Histones/genetics/*metabolism
MH  - Homeodomain Proteins/genetics/metabolism
MH  - Humans
MH  - Lysine/genetics/*metabolism
MH  - Methylation
MH  - Methyltransferases/genetics/metabolism
MH  - Mice
MH  - Mutation
MH  - Protein Transport
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Repressor Proteins/genetics/metabolism
MH  - Signal Transduction
PMC - PMC3668625
EDAT- 2013/04/13 06:00
MHDA- 2013/08/24 06:00
PMCR- 2013/04/01
CRDT- 2013/04/13 06:00
PHST- 2013/04/13 06:00 [entrez]
PHST- 2013/04/13 06:00 [pubmed]
PHST- 2013/08/24 06:00 [medline]
PHST- 2013/04/01 00:00 [pmc-release]
AID - cddis201398 [pii]
AID - 10.1038/cddis.2013.98 [doi]
PST - epublish
SO  - Cell Death Dis. 2013 Apr 11;4(4):e583. doi: 10.1038/cddis.2013.98.