TY - CHAP
T1 - CTCF binding at the H19 imprinting control region mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to Igf2
AU - Kurukuti, Sreenivasulu
AU - Tiwari, Vijay Kumar
AU - Tavoosidana, Gholamreza
AU - Pugacheva, Elena
AU - Murrell, Adele
AU - Zhao, Zhihu
AU - Lobanenkov, Victor
AU - Reik, Wolf
AU - Ohlsson, Rolf
PY - 2006
Y1 - 2006
N2 - It is thought that the H19 imprinting control region (ICR) directs the silencing of the maternally inherited Igf2 allele through a CTCF-dependent chromatin insulator. The ICR has been shown to interact physically with a silencer region in Igf2, differentially methylated region (DMR)1, but the role of CTCF in this chromatin loop and whether it restricts the physical access of distal enhancers to Igf2 is not known. We performed systematic chromosome conformation capture analyses in the Igf2/H19 region over >160 kb, identifying sequences that interact physically with the distal enhancers and the ICR. We found that, on the paternal chromosome, enhancers interact with the Igf2 promoters but that, on the maternal allele, this is prevented by CTCF binding within the H19 ICR. CTCF binding in the maternal ICR regulates its interaction with matrix attachment region (MAR)3 and DMR1 at Igf2, thus forming a tight loop around the maternal Igf2 locus, which may contribute to its silencing. Mutation of CTCF binding sites in the H19 ICR leads to loss of CTCF binding and de novo methylation of a CTCF target site within Igf2 DMR1, showing that CTCF can coordinate regional epigenetic marks. This systematic chromosome conformation capture analysis of an imprinting cluster reveals that CTCF has a critical role in the epigenetic regulation of higher-order chromatin structure and gene silencing over considerable distances in the genome.
AB - It is thought that the H19 imprinting control region (ICR) directs the silencing of the maternally inherited Igf2 allele through a CTCF-dependent chromatin insulator. The ICR has been shown to interact physically with a silencer region in Igf2, differentially methylated region (DMR)1, but the role of CTCF in this chromatin loop and whether it restricts the physical access of distal enhancers to Igf2 is not known. We performed systematic chromosome conformation capture analyses in the Igf2/H19 region over >160 kb, identifying sequences that interact physically with the distal enhancers and the ICR. We found that, on the paternal chromosome, enhancers interact with the Igf2 promoters but that, on the maternal allele, this is prevented by CTCF binding within the H19 ICR. CTCF binding in the maternal ICR regulates its interaction with matrix attachment region (MAR)3 and DMR1 at Igf2, thus forming a tight loop around the maternal Igf2 locus, which may contribute to its silencing. Mutation of CTCF binding sites in the H19 ICR leads to loss of CTCF binding and de novo methylation of a CTCF target site within Igf2 DMR1, showing that CTCF can coordinate regional epigenetic marks. This systematic chromosome conformation capture analysis of an imprinting cluster reveals that CTCF has a critical role in the epigenetic regulation of higher-order chromatin structure and gene silencing over considerable distances in the genome.
KW - Animals
KW - DNA-Binding Proteins
KW - DNA-Binding Proteins: metabolism
KW - DNA-Binding Proteins: physiology
KW - Enhancer Elements
KW - Epigenesis
KW - Female
KW - Gene Silencing
KW - Genetic
KW - Genetic: physiology
KW - Genomic Imprinting
KW - Genomic Imprinting: physiology
KW - Heterochromatin
KW - Heterochromatin: chemistry
KW - Heterochromatin: genetics
KW - Heterochromatin: metabolism
KW - Insulin-Like Growth Factor II
KW - Insulin-Like Growth Factor II: genetics
KW - Insulin-Like Growth Factor II: metabolism
KW - Long Noncoding
KW - Male
KW - Mice
KW - Protein Binding
KW - Protein Binding: genetics
KW - Protein Conformation
KW - Proteins
KW - Proteins: genetics
KW - RNA
KW - Repressor Proteins
KW - Repressor Proteins: metabolism
KW - Repressor Proteins: physiology
KW - Untranslated
KW - Untranslated: metabolism
KW - Untranslated: physiology
UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1484419&tool=pmcentrez&rendertype=abstract
http://www.pnas.org/cgi/doi/10.1073/pnas.0600326103
UR - http://www.mendeley.com/research/ctcf-binding-h19-imprinting-control-region-mediates-maternally-inherited-higherorder-chromatin-confo
U2 - 10.1073/pnas.0600326103
DO - 10.1073/pnas.0600326103
M3 - Chapter
C2 - 16815976
SN - 0027-8424 (Print)
T3 - Proceedings of the National Academy of Sciences
SP - 10684
EP - 10689
BT - Proceedings of the National Academy of Sciences
ER -