D86 Nucleic Acids Research, 2008, Vol. 36, Database issue Figure 2. A CTCF-binding site (INSUL_MAN0004) webpage displays the ﬂanking gene expression proﬁles and links to tracks of SNPs, genomic context and orthologous regions. between query sequences and CTCF-binding sequences. Finally, an option of genomic range search is provided. Users can specify a genomic interval and retrieve all the CTCF-binding sites in the interval. To maintain an up-to-date resource, we encourage researchers to submit newly identiﬁed CTCFBS sequences to the database. Data can be submitted directly through a web interface. The submissions will be manually checked before being added to the database. The database is an integrative platform for storing, retrieving and characterizing vertebrate genomic insulators. We envision that with more and more experimentally validated CTCFBS sequences available in the database, a comprehensive analysis of these sequences may facilitate the extraction of meaningful sequence signals, uncover the functional basis of insulators, and ultimately enable the mapping of every distinct transcrip- tion domain along the genomes. ACKNOWLEDGEMENTS We thank Dr Bing Ren for providing the 20-bp motif information for 13 801 experimentally identiﬁed CTCF-binding sites, Drs Bing Ren, Xiaohui Xie and Eric S. Lander for providing the predicted CTCF motifs and Dr Keji Zhao for providing the genomic coordinates of 20 262 CTCF-binding sites. Funding to pay the Open Access publication charges for this article was provided by The University of Tennessee Health Science Center. Conﬂict of interest statement. None declared. REFERENCES 1. Moon,H., Filippova,G., Loukinov,D., Pugacheva,E., Chen,Q., Smith,S.T., Munhall,A., Grewe,B., Bartkuhn,M. et al. (2005) CTCF is conserved from Drosophila to humans and confers enhancer blocking of the Fab-8 insulator. EMBO Rep., 6, 165–170. 2. West,A.G., Gaszner,M. and Felsenfeld,G. (2002) Insulators: many functions, many mechanisms. Genes Dev., 16, 271–288. 3. Bell,A.C., West,A.G. and Felsenfeld,G. (2001) Insulators and boundaries: versatile regulatory elements in the eukaryotic. Science, 291, 447–450. 4. Gaszner,M. and Felsenfeld,G. (2006) Insulators: exploiting transcriptional and epigenetic mechanisms. Nat. Rev. Genet., 7, 703–713. 5. Kuhn,E.J. and Geyer,P.K. (2003) Genomic insulators: connecting properties to mechanism. Curr. Opin. Cell Biol., 15, 259–265. 6. Brasset,E. and Vaury,C. (2005) Insulators are fundamental components of the eukaryotic genomes. Heredity, 94, 571–576. 7. Capelson,M. and Corces,V.G. (2004) Boundary elements and nuclear organization. Biol. Cell, 96, 617–629. 8. Engel,N. and Bartolomei,M.S. (2003) Mechanisms of insulator function in gene regulation and genomic imprinting. Int. Rev. Cytol., 232, 89–127. 9. Fourel,G., Magdinier,F. and Gilson,E. (2004) Insulator dynamics and the setting of chromatin domains. Bioessays, 26, 523–532. 10. Geyer,P.K. and Clark,I. (2002) Protecting against promiscuity: the regulatory role of insulators. Cell Mol. Life Sci., 59, 2112–2127. 11. Labrador,M. and Corces,V.G. (2002) Setting the boundaries of chromatin domains and nuclear organization. Cell, 111, 151–154. 12. West,A.G. and Fraser,P. (2005) Remote control of gene transcription. Hum. Mol. Genet., 14, R101–R111. 13. Scott,K.C., Merrett,S.L. and Willard,H.F. (2006) A heterochromatin barrier partitions the ﬁssion yeast centromere into discrete chromatin domains. Curr. Biol., 16, 119–129.