PMID- 10839547
OWN - NLM
STAT- MEDLINE
DCOM- 20000616
LR  - 20240104
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 405
IP  - 6785
DP  - 2000 May 25
TI  - CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 
      locus.
PG  - 486-9
AB  - The Insulin-like growth factor 2 (Igf2) and H19 genes are imprinted, resulting in 
      silencing of the maternal and paternal alleles, respectively. This event is 
      dependent upon an imprinted-control region two kilobases upstream of H19 (refs 1, 
      2). On the paternal chromosome this element is methylated and required for the 
      silencing of H19 (refs 2-4). On the maternal chromosome the region is 
      unmethylated and required for silencing of the Igf2 gene 90 kilobases upstream. 
      We have proposed that the unmethylated imprinted-control region acts as a 
      chromatin boundary that blocks the interaction of Igf2 with enhancers that lie 3' 
      of H19 (refs 5, 6). This enhancer-blocking activity would then be lost when the 
      region was methylated, thereby allowing expression of Igf2 paternally. Here we 
      show, using transgenic mice and tissue culture, that the unmethylated 
      imprinted-control regions from mouse and human H19 exhibit enhancer-blocking 
      activity. Furthermore, we show that CTCF, a zinc finger protein implicated in 
      vertebrate boundary function, binds to several sites in the unmethylated 
      imprinted-control region that are essential for enhancer blocking. Consistent 
      with our model, CTCF binding is abolished by DNA methylation. This is the first 
      example, to our knowledge, of a regulated chromatin boundary in vertebrates.
FAU - Hark, A T
AU  - Hark AT
AD  - Howard Hughes Medical Institute and Department of Molecular Biology, Princeton 
      University, New Jersey 08544, USA.
FAU - Schoenherr, C J
AU  - Schoenherr CJ
FAU - Katz, D J
AU  - Katz DJ
FAU - Ingram, R S
AU  - Ingram RS
FAU - Levorse, J M
AU  - Levorse JM
FAU - Tilghman, S M
AU  - Tilghman SM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (CCCTC-Binding Factor)
RN  - 0 (CTCF protein, human)
RN  - 0 (Ctcf protein, mouse)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (H19 long non-coding RNA)
RN  - 0 (Muscle Proteins)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Untranslated)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 67763-97-7 (Insulin-Like Growth Factor II)
RN  - 9007-49-2 (DNA)
SB  - IM
CIN - Nature. 2000 May 25;405(6785):408-9. PMID: 10839521
MH  - Animals
MH  - CCCTC-Binding Factor
MH  - Cell Line
MH  - DNA/metabolism
MH  - *DNA Methylation
MH  - DNA-Binding Proteins/*physiology
MH  - *Enhancer Elements, Genetic
MH  - *Gene Expression Regulation
MH  - Genomic Imprinting
MH  - Humans
MH  - Insulin-Like Growth Factor II/*genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Muscle Proteins/*genetics
MH  - Protein Binding
MH  - RNA, Long Noncoding
MH  - *RNA, Untranslated
MH  - Regulatory Sequences, Nucleic Acid
MH  - *Repressor Proteins
MH  - Transcription Factors/*physiology
MH  - Zinc Fingers
EDAT- 2000/06/06 09:00
MHDA- 2000/06/24 11:00
CRDT- 2000/06/06 09:00
PHST- 2000/06/06 09:00 [pubmed]
PHST- 2000/06/24 11:00 [medline]
PHST- 2000/06/06 09:00 [entrez]
AID - 10.1038/35013106 [doi]
PST - ppublish
SO  - Nature. 2000 May 25;405(6785):486-9. doi: 10.1038/35013106.