Communication of genome regulatory elements in a folded chromosome

Abstract

a b s t r a c tThe most popular model of gene activation by remote enhancers postulates that the enhancers interact directly with target promoters via the looping of intervening DNA fragments. This interaction is thought to be necessary for the stabilization of the Pol II pre-initiation complex and/or for the transfer of transcription factors and Pol II, which are initially accumulated at the enhancer, to the promoter. The direct interaction of enhancer(s) and promoter(s) is only possible when these elements are located in close proximity within the nuclear space. Here, we discuss the molecular mechanisms for maintaining the close proximity of the remote regulatory elements of the eukaryotic genome. The models of an active chromatin hub (ACH) and an active nuclear compartment are considered, focusing on the role of chromatin folding in juxtaposing remote DNA sequences. The interconnection between the functionally dependent architecture of the interphase chromosome and nuclear compartmentalization is also discussed.

Conserved Higher-Order Chromatin Regulates NMDA Receptor Gene Expression and Cognition

“…Importantly, chromosomal loop formations are critical for this layer of transcriptional regulation, because many distal regulatory elements typically only become effective when placed in close spatial proximity to the transcription start sites of their target gene(Levine et al, 2014). Loop formations—which often require CTCF-binding factor, cohesins and various other proteins assembled into scaffolds and anchors(Razin et al, 2013)—potentially bypass many kilo- (Kb) or even megabases (Mb) of linear genome, thereby repositioning promoter-distal regulatory elements next to their target promoters and TSSs (Gaszner and Felsenfeld, 2006; Wood et al, 2010). …”

Dynamic Estrogen Receptor Interactomes Control Estrogen-Responsive Trefoil Factor (TFF) Locus Cell-Specific Activities

“…n mammals, gene transcription relies on complex and highly organized regulatory processes, which include binding of transcription factors to cognate DNA sequences (cis elements), chromatin structure and epigenetic information, the action of additional factors in trans (cofactors and RNA polymerase II [Pol II] machinery), and the spatial organization of the genome (1)(2)(3)(4)(5). Signaling pathways initiated by steroid hormones, such as 17␤-estradiol (E2), provide model systems to study these different layers of transcription regulation in mammalian cells.…”

3D genomics imposes evolution of the domain model of eukaryotic genome organization

“…However, current studies demonstrate that the genome is spatially organized in a functionally dependent way (reviewed in Dekker and Mirny 2016;Rowley and Corces 2016). In particular, remote regulatory elements may be clustered in the nuclear space or even assembled in a common regulatory complex (reviewed in de Laat and Grosveld 2003;Pombo and Dillon 2015;Razin et al 2013;Sexton and Cavalli 2015). Consequently, genomic domains that are split on DNA may regain their integrity due to their spatial organization within the nuclear space.…”