PMID- 20417597
OWN - NLM
STAT- MEDLINE
DCOM- 20100510
LR  - 20211020
IS  - 1097-4164 (Electronic)
IS  - 1097-2765 (Print)
IS  - 1097-2765 (Linking)
VI  - 38
IP  - 2
DP  - 2010 Apr 23
TI  - CpG islands recruit a histone H3 lysine 36 demethylase.
PG  - 179-90
LID - 10.1016/j.molcel.2010.04.009 [doi]
AB  - In higher eukaryotes, up to 70% of genes have high levels of nonmethylated 
      cytosine/guanine base pairs (CpGs) surrounding promoters and gene regulatory 
      units. These features, called CpG islands, were identified over 20 years ago, but 
      there remains little mechanistic evidence to suggest how these enigmatic elements 
      contribute to promoter function, except that they are refractory to epigenetic 
      silencing by DNA methylation. Here we show that CpG islands directly recruit the 
      H3K36-specific lysine demethylase enzyme KDM2A. Nucleation of KDM2A at these 
      elements results in removal of H3K36 methylation, creating CpG island chromatin 
      that is uniquely depleted of this modification. KDM2A utilizes a zinc finger CxxC 
      (ZF-CxxC) domain that preferentially recognizes nonmethylated CpG DNA, and 
      binding is blocked when the CpG DNA is methylated, thus constraining KDM2A to 
      nonmethylated CpG islands. These data expose a straightforward mechanism through 
      which KDM2A delineates a unique architecture that differentiates CpG island 
      chromatin from bulk chromatin.
CI  - Copyright 2010 Elsevier Inc. All rights reserved.
FAU - Blackledge, Neil P
AU  - Blackledge NP
AD  - Department of Biochemistry, University of Oxford, Oxford, UK.
FAU - Zhou, Jin C
AU  - Zhou JC
FAU - Tolstorukov, Michael Y
AU  - Tolstorukov MY
FAU - Farcas, Anca M
AU  - Farcas AM
FAU - Park, Peter J
AU  - Park PJ
FAU - Klose, Robert J
AU  - Klose RJ
LA  - eng
SI  - GEO/GSE21202
GR  - WT_/Wellcome Trust/United Kingdom
GR  - R01GM082798/GM/NIGMS NIH HHS/United States
GR  - R01 GM082798/GM/NIGMS NIH HHS/United States
GR  - MRC_/Medical Research Council/United Kingdom
GR  - CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell
JT  - Molecular cell
JID - 9802571
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (F-Box Proteins)
RN  - 0 (Histones)
RN  - 0 (Recombinant Proteins)
RN  - EC 1.14.11.- (Histone Demethylases)
RN  - EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases)
RN  - EC 1.14.11.27 (KDM2A protein, human)
RN  - EC 1.5.- (Oxidoreductases, N-Demethylating)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites/genetics
MH  - CpG Islands/*genetics
MH  - DNA Methylation
MH  - DNA-Binding Proteins/metabolism
MH  - F-Box Proteins
MH  - Histone Demethylases/*metabolism
MH  - Histones/chemistry/*metabolism
MH  - Humans
MH  - Jumonji Domain-Containing Histone Demethylases
MH  - Lysine/chemistry/*metabolism
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Oxidoreductases, N-Demethylating/chemistry/genetics/*metabolism
MH  - Protein Binding/genetics
MH  - Protein Structure, Tertiary
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Sequence Homology, Amino Acid
PMC - PMC3098377
EDAT- 2010/04/27 06:00
MHDA- 2010/05/11 06:00
PMCR- 2010/04/23
CRDT- 2010/04/27 06:00
PHST- 2010/01/11 00:00 [received]
PHST- 2010/02/26 00:00 [revised]
PHST- 2010/04/06 00:00 [accepted]
PHST- 2010/04/27 06:00 [entrez]
PHST- 2010/04/27 06:00 [pubmed]
PHST- 2010/05/11 06:00 [medline]
PHST- 2010/04/23 00:00 [pmc-release]
AID - S1097-2765(10)00286-8 [pii]
AID - 10.1016/j.molcel.2010.04.009 [doi]
PST - ppublish
SO  - Mol Cell. 2010 Apr 23;38(2):179-90. doi: 10.1016/j.molcel.2010.04.009.