Chromatin insulators and cohesins

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Abstract
Chromatin insulators have evolved to regulate transcription by using regulatory elements that are often distant from each other on the linear genome. This feature is position‐dependent—that is, a functional insulator must be positioned between the enhancer and its target promoter (Wallace & Felsenfeld, 2007). The molecular basis of insulation seems to be tightly linked to, and might depend on, several long‐range physical interactions between different portions of the chromatin fibre (Wallace & Felsenfeld, 2007). This is exemplified by the H19 imprinting control region, which not only regulates long‐range interactions but also the epigenetic states of a crucial cis element (Kurukuti et al , 2006). Independent suggestions have promoted the idea that components of the cohesin complex might participate in the formation of such complexes and contribute to the insulator function (Hagstrom & Meyer, 2003). This proposal has been partly borne out in three seminal reports published in recent issues of Nature (Wendt et al , 2008), Cell (Parelho et al , 2008) and The EMBO Journal (Stedman et al , 2008). Although the full implications of these observations remain to be elucidated, they have shed new light on how the enigmatic chromatin insulators might operate. How do the cohesins work and how are they organized? The cohesin complex comprises four components termed Smc1, Smc3, Scc3 and Scc1 (Smc for structural maintenance of chromosomes; Scc for Subunit of the cohesin complex), also known as Rad21. It has been proposed that Smc1 and Smc3 form a heterodimer together with Scc1, and that Scc3 organizes a ring structure. In addition, Scc2 and Scc4 are required for the loading of the cohesin complex onto the chromatin fibre. Functionally, the cohesin complex holds sister chromatids together after DNA replication until their sequential separation during G2/M phases. This function is essential for genomic DNA stability and repair (for reviews, see …