PMID- 24081332
OWN - NLM
STAT- MEDLINE
DCOM- 20140107
LR  - 20211021
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 33
IP  - 23
DP  - 2013 Dec
TI  - The MLL3/MLL4 branches of the COMPASS family function as major histone H3K4 
      monomethylases at enhancers.
PG  - 4745-54
LID - 10.1128/MCB.01181-13 [doi]
AB  - Histone H3 lysine 4 (H3K4) can be mono-, di-, and trimethylated by members of the 
      COMPASS (complex of proteins associated with Set1) family from Saccharomyces 
      cerevisiae to humans, and these modifications can be found at distinct regions of 
      the genome. Monomethylation of histone H3K4 (H3K4me1) is relatively more enriched 
      at metazoan enhancer regions compared to trimethylated histone H3K4 (H3K4me3), 
      which is enriched at transcription start sites in all eukaryotes. Our recent 
      studies of Drosophila melanogaster demonstrated that the Trithorax-related (Trr) 
      branch of the COMPASS family regulates enhancer activity and is responsible for 
      the implementation of H3K4me1 at these regions. There are six COMPASS family 
      members in mammals, two of which, MLL3 (GeneID 58508) and MLL4 (GeneID 8085), are 
      most closely related to Drosophila Trr. Here, we use chromatin 
      immunoprecipitation-sequencing (ChIP-seq) of this class of COMPASS family members 
      in both human HCT116 cells and mouse embryonic stem cells and find that MLL4 is 
      preferentially found at enhancer regions. MLL3 and MLL4 are frequently mutated in 
      cancer, and indeed, the widely used HCT116 cancer cell line contains inactivating 
      mutations in the MLL3 gene. Using HCT116 cells in which MLL4 has also been 
      knocked out, we demonstrate that MLL3 and MLL4 are major regulators of H3K4me1 in 
      these cells, with the greatest loss of monomethylation at enhancer regions. 
      Moreover, we find a redundant role between Mll3 (GeneID 231051) and Mll4 (GeneID 
      381022) in enhancer H3K4 monomethylation in mouse embryonic fibroblast (MEF) 
      cells. These findings suggest that mammalian MLL3 and MLL4 function in the 
      regulation of enhancer activity and that mutations of MLL3 and MLL4 that are 
      found in cancers could exert their properties through malfunction of these 
      Trr/MLL3/MLL4-specific (Trrific) enhancers.
FAU - Hu, Deqing
AU  - Hu D
AD  - Stowers Institute for Medical Research, Kansas City, Missouri, USA.
FAU - Gao, Xin
AU  - Gao X
FAU - Morgan, Marc A
AU  - Morgan MA
FAU - Herz, Hans-Martin
AU  - Herz HM
FAU - Smith, Edwin R
AU  - Smith ER
FAU - Shilatifard, Ali
AU  - Shilatifard A
LA  - eng
GR  - R01 CA150265/CA/NCI NIH HHS/United States
GR  - R01CA150265/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130930
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Histones)
RN  - 0 (KMT2C protein, human)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 2.1.1.43 (MLL4 protein, human)
SB  - IM
MH  - Animals
MH  - DNA-Binding Proteins/*physiology
MH  - *Enhancer Elements, Genetic
MH  - Epigenesis, Genetic
MH  - Gene Expression
MH  - HCT116 Cells
MH  - Histone-Lysine N-Methyltransferase
MH  - Histones/*metabolism
MH  - Humans
MH  - Methylation
MH  - Mice
MH  - Neoplasms/genetics/metabolism
MH  - *Protein Processing, Post-Translational
MH  - Protein Transport
PMC - PMC3838007
EDAT- 2013/10/02 06:00
MHDA- 2014/01/08 06:00
PMCR- 2014/06/01
CRDT- 2013/10/02 06:00
PHST- 2013/10/02 06:00 [entrez]
PHST- 2013/10/02 06:00 [pubmed]
PHST- 2014/01/08 06:00 [medline]
PHST- 2014/06/01 00:00 [pmc-release]
AID - MCB.01181-13 [pii]
AID - 01181-13 [pii]
AID - 10.1128/MCB.01181-13 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2013 Dec;33(23):4745-54. doi: 10.1128/MCB.01181-13. Epub 2013 Sep 
      30.