Nonallelic transvection of multiple imprinted loci is organized by the H19 imprinting control region during germline development

Abstract

Recent observations highlight that the mammalian genome extensively communicates with itself via longrange chromatin interactions. The causal link between such chromatin cross-talk and epigenetic states is, however, poorly understood. We identify here a network of physically juxtaposed regions from the entire genome with the common denominator of being genomically imprinted. Moreover, CTCF-binding sites within the H19 imprinting control region (ICR) not only determine the physical proximity among imprinted domains, but also transvect allele-specific epigenetic states, identified by replication timing patterns, to interacting, nonallelic imprinted regions during germline development. We conclude that one locus can directly or indirectly pleiotropically influence epigenetic states of multiple regions on other chromosomes with which it interacts.Supplemental material is available at http://www.genesdev.org.

The Strategies of the Genes: Genomic Conflicts, Attachment Theory, and Development of the Social Brain

“…Such interactions occur genome-wide (Ling and Hoffman 2007), but are strongly enriched to imprinted regions (Zhao et al 2006), with an 7 apparent central role for the imprinted RNA gene H19 as a hub for transvection of parent-of-origin specific effects to both imprinted and non-imprinted loci on other chromosomes (Sandhu et al 2009). Inter-chromosomal interactions that involve imprinted loci provide a genome-scale mechanism for coordinated expression of imprinted genes (in addition to mechanisms involving, for example, transcription factors such as Zac1, and protein-protein interactions such as those between p57kip2 and Nurr1) (Joseph et al 2003), and for control of non-imprinted genes and loci by specific imprinted genes, that may serve to increase their relative influence on development.…”

The strategic gene

“…As another example, the imprinted H19 gene interacts directly (without RNA intermediates) with imprinted regions on other chromosomes and influences when in the cell cycle these other genes are replicated (Sandhu et al 2009). …”

The Capacity to Act in Trans Varies Among Drosophila Enhancers

“…In contrast, the genetic impacts of trans-interactions between chromosomes are less clearly understood. Examples of gene regulation involving interchromosomal associations have been described (Spilianakis et al 2005;Bacher et al 2006;Xu et al 2006;Apostolou and Thanos 2008;Sandhu et al 2009;Markenscoff-Papadimitriou et al 2014;Patel et al 2014), but it remains unclear whether it is common for sequences that regulate gene expression to communicate between different chromosomes when they are physically juxtaposed.In Drosophila melanogaster, extensive trans-interactions are observed between homologous chromosomes in virtually all somatic tissues, a phenomenon known as somatic homolog pairing (reviewed by McKee 2004;Bosco 2012). The close proximity of homologous chromosomes in Drosophila can permit an enhancer to act in trans on a promoter on the paired homolog, a form of pairing-dependent gene regulation called transvection (Lewis 1954).…”

“…In contrast, the genetic impacts of trans-interactions between chromosomes are less clearly understood. Examples of gene regulation involving interchromosomal associations have been described (Spilianakis et al 2005;Bacher et al 2006;Xu et al 2006;Apostolou and Thanos 2008;Sandhu et al 2009;Markenscoff-Papadimitriou et al 2014;Patel et al 2014), but it remains unclear whether it is common for sequences that regulate gene expression to communicate between different chromosomes when they are physically juxtaposed.…”