Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells

By Stefan Schoenfelder, Tom Sexton, L. Chakalova, Nathan F. Cope, Alice Horton, Simon R. Andrews, Sreenivasulu Kurukuti, Jennifer A. Mitchell, David Umlauf, D. Dimitrova and 6 more. Nature Genetics, 2009

749 citations recorded by the source corpus.

The discovery of interchromosomal interactions in higher eukaryotes points to a functional interplay between genome architecture and gene expression, challenging the view of transcription as a one-dimensional process. However, the extent of interchromosomal interactions and the underlying mechanisms are unknown. Here we present the first genome-wide analysis of transcriptional interactions using the mouse globin genes in erythroid tissues. Our results show that the active globin genes associate with hundreds of other transcribed genes, revealing extensive and preferential intra- and interchromosomal transcription interactomes. We show that the transcription factor Klf1 mediates preferential co-associations of Klf1-regulated genes at a limited number of specialized transcription factories. Our results establish a new gene expression paradigm, implying that active co-regulated genes and their regulatory factors cooperate to create specialized nuclear hot spots optimized for efficient and coordinated transcriptional control.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7512e0a877df0a323b9f8d4615badaa2f646f263

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Citations in the corpus

A decade of 3C technologies: insights into nuclear organization. (2012, background): “A modified 4C approach to study the DNA interactions of the active b-globin and a-globin loci led to the conclusion that coregulated genes preferentially meet at dedicated transcription sites in the nucleus (Schoenfelder et al. 2010).”
GREAT improves functional interpretation of cis-regulatory regions (2010, background): “The top two ontology terms suggest limb-specific expression during Theiler stage 19 (TS19), which corresponds precisely with embryonic day 11.5, the time point at which the p300 limb peaks were assayed in ref.”
Extensive Promoter-centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation (2012, neutral): “…only 1,328 multigene complexes in this combined pilot dataset, 11,723 genes were engaged in these complexes for an average of 8.8 genes per interaction complex (Figure 1D), indicating that promoter-promoter interactions were widespread and may play a significant role in transcription regulation.”
Functional and mechanistic diversity of distal transcription enhancers (2011, neutral): “In fact, some studies have suggested that transcription factories occur in different varieties, corresponding to transcription mediated by different factors (Xu and Cook, 2008; Schoenfelder et al., 2010).”
Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data (2013, background): “This implies that actively transcribed genes tend to co-localize, possibly in specific groups related to their transcriptional regulators 13 .”
Probabilistic modeling of Hi-C contact maps eliminates systematic biases to characterize global chromosomal architecture (2011, methodology): “Chromosomal organization has therefore been explored for many decades using methods that vary in scale and resolutio”
Charting histone modifications and the functional organization of mammalian genomes (2011, background): “Together with ongoing studies of additional structures, such as transcription factories and nucleolus-associated domain”
CTCF-Mediated Functional Chromatin Interactome in Pluripotent Cells (2011, background): “Therefore, the elucidation of the three-dimensional chromatin interactome is essential for understanding genome organization in lineage specification and transcription regulatio”
Enhancer function: new insights into the regulation of tissue-specific gene expression (2011, positive): “The KLF1 transcription factor, which binds both enhancer and promoter elements, is necessary for mediating preferential co-associations of KLF1-regulated genes at a limited number of specialized transcription factorie”
Three-dimensional folding and functional organization principles of the Drosophila genome. (2012, background): “These networks involve transcriptionally active genes (Apostolou and Thanos, 2008; Hu et al., 2008; Noordermeer et al., 2011; Schoenfelder et al., 2010; Simonis et al., 2006), imprinted genes (Zhao et al., 2006), or genes repressed by Polycomb group (PcG) proteins (Bantignies et al., 2011; Tolhuis…”
Architectural protein subclasses shape 3D organization of genomes during lineage commitment. (2013, neutral): “Principles from these studies have been difficult to generalize, however, because most previous reports focus on interrogation of 3D interactions between specific preselected fragments (Kurukuti et al., 2006; Noordermeer et al., 2011; Schoenfelder et al., 2010; Vakoc et al., 2005).”