The Drosophila homolog of the mammalian imprint regulator, CTCF, maintains the maternal genomic imprint in Drosophila me
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RESEARCH ARTICLE
Open Access
The Drosophila homolog of the mammalian imprint regulator, CTCF, maintains the maternal genomic imprint in Drosophila melanogaster William A MacDonald1*, Debashish Menon2, Nicholas J Bartlett3, G Elizabeth Sperry3, Vanya Rasheva2,4, Victoria Meller2, Vett K Lloyd3*
Abstract Background: CTCF is a versatile zinc finger DNA-binding protein that functions as a highly conserved epigenetic transcriptional regulator. CTCF is known to act as a chromosomal insulator, bind promoter regions, and facilitate long-range chromatin interactions. In mammals, CTCF is active in the regulatory regions of some genes that exhibit genomic imprinting, acting as insulator on only one parental allele to facilitate parent-specific expression. In Drosophila, CTCF acts as a chromatin insulator and is thought to be actively involved in the global organization of the genome. Results: To determine whether CTCF regulates imprinting in Drosophila, we generated CTCF mutant alleles and assayed gene expression from the imprinted Dp(1;f)LJ9 mini-X chromosome in the presence of reduced CTCF expression. We observed disruption of the maternal imprint when CTCF levels were reduced, but no effect was observed on the paternal imprint. The effect was restricted to maintenance of the imprint and was specific for the Dp(1;f)LJ9 mini-X chromosome. Conclusions: CTCF in Drosophila functions in maintaining parent-specific expression from an imprinted domain as it does in mammals. We propose that Drosophila CTCF maintains an insulator boundary on the maternal X chromosome, shielding genes from the imprint-induced silencing that occurs on the paternally inherited X chromosome. See commentary: http://www.biomedcentral.com/1741-7007/8/104
Background The correct establishment and propagation of epigenetic states are essential for normal development, and disruption of these processes leads to disease. Genomic imprinting is a striking example of the effect of epigenetics on gene regulation. In genomic imprinting, a mark, the imprint, is imposed on the two parental genomes during gametogenesis. In the zygote, the imprint is maintained through each mitotic division and results in the parental alleles of a gene, or entire homologous chromosomes, adopting different epigenetic states. As a result of these different epigenetic states, one parental * Correspondence: [email protected]; [email protected] 1 Department of Biology, Dalhousie University, Halifax, Nova Scotia, Canada 3 Department of Biology, Mt. Allison University, Sackville, New Brunswick, Canada Full list of author information is available at the end of the article
allele can be silenced while the allele from the other parent, although identical in DNA sequence, is active. The CCCTC-binding factor, CTCF, is a key player in maintaining epigenetically distinct chromatin domains. CTCF is an evolutionarily conserved zinc finger-containing DNA-binding protein that can function both directly in gene regulation as a transcription factor and also indirectly by mediating long-range chromatin interact
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