Insulators and imprinting from flies to mammals

Abstract

The nuclear factor CTCF has been shown to be necessary for the maintenance of genetic imprinting at the mammalian H19/Igf2 locus. MacDonald and colleagues now report in BMC Biology that the mechanisms responsible for maintaining the imprinted state in Drosophila may be evolutionarily conserved and that CTCF may also play a critical role in this process. See research article http://www.biomedcentral.com/1741-7007/8/105.

Figure 1

Possible models to explain the role of dCTCF in the maintenance of imprinting in Drosophila. In all panels, a hypothetical transcription factor (TF) controlling the expression of the garnet gene is shown as a red oval; the garnet gene is represented as a green arrow, which is dashed when the gene is subject to silencing by heterochromatin and solid when it is expressed normally; dCTCF is represented by a blue oval; nucleosomes are shown as yellow circles; and DNA is in black. (a) dCTCF in the maternal chromosome forms a barrier against the spreading of heterochromatin, leading to normal expression of the adjacent gene; presumably, CTCF is not present in the paternal chromosome and heterochromatin spreads into the gene. (b) dCTCF, either directly or in combination with other factors, affects the transcription of the garnet gene, antagonizing the spreading of heterochromatin and overcoming its silencing effect. (c) An alternative explanation that involves the formation of a loop between a dCTCF site adjacent to the heterochromatin and a second site somewhere else in the genome. The garnet gene and its regulatory sequences are located inside of the loop, which protects the gene against heterochromatin silencing. The models in (a,c) are conceptually similar but mechanistically different and the latter is more in line with observations in mammals.