Loop formation through intra- and inter-chromosomal interactions is a common strategy for genome organization and insulation in different organisms. (a) In Drosophila, the Su(Hw) protein binds to specific DNA elements and recruits the CP190 protein and Mod(mdg4)2.2 proteins. Interaction among these proteins results in the formation of chromatin loops. Mod(mdg4)2.2 attaches the chromatin to the nuclear periphery through its interaction with topoisomerase I-interacting RS protein (dTopors). (b) Monoallelic expression at the Igf2-H19 locus is regulated by binding of CTCF to the imprinted control region (ICR). On the maternal allele, CTCF mediates interactions between ICR and DNA methylated region 1 (DMR1) that also involve joining of the DNA strands by cohesin, insulating Igf2 from the influence of downstream enhancers. Methylated ICR sequences prevent CTCF from binding to the ICR on the paternal allele, allowing downstream enhancers to switch on Igf2 transcription. (c) In S. pombe, TFIIIC binds to RNA polymerase (Pol) III at tRNA genes and acts as a barrier against the spreading of heterochromatin. It is also hypothesized to organize the chromatin into distinct loops by clustering various chromosome-organizing clamp (COC) loci to the nuclear periphery. (d) In A. thaliana, binding of the ASYMMETRIC LEAVES1 (AS1)-AS2 complex at two specific DNA sites flanking the enhancer is required to silence the expression of the BP gene. Recruitment of the histone chaperone HIRA is necessary for this process, and it probably acts by facilitating looping of the enhancer element.