![]() ![]() Mammalian genomes have roughly one thousand of such lamina-associated domains (LADs), which are typically hundreds of kb or even a few Mb in size. The NL contacts of some LADs are highly consistent between cell types, while other LADs interact in cell-type-specific (facultative) manners with the NL. How LAD-NL contacts are regulated is poorly understood. Most genes inside LADs have very low transcriptional activity (Guelen et al, 2008 Peric-Hupkes et al, 2010 Leemans et al, 2019). When cells differentiate, detachment of genes from the NL often coincides with transcriptional activation, while increased NL interactions correlate with reduced transcription (Peric-Hupkes et al, 2010 Lund et al, 2013 Robson et al, 2016, 2017). These observations raise the interesting possibility that the NL helps to establish a repressive environment. In support of this notion, depletion of lamins can lead to derepression of specific genes (primarily in Drosophila) (Shevelyov et al, 2009 Kohwi et al, 2013 Chen et al, 2014) transfer of human inactive promoters from LADs to a neutral chromatin environment can lead to activation of these promoters (Leemans et al, 2019) and artificial tethering of some genes to the NL can reduce their activity (Finlan et al, 2008 Kumaran & Spector, 2008 Reddy et al, 2008 Dialynas et al, 2010). This, however, does not rule out that the contacts of genes with the NL are the consequence of a lack of transcriptional activity, and vice versa, that genes detach from the NL in response to their activation. This was initially suggested by experiments with fluorescently tagged lacO arrays that were integrated in a locus near the NL. Tethering of the transcriptional activator peptide VP16 to these arrays caused repositioning away from the NL (Tumbar & Belmont, 2001). ![]()
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