Integrating one-dimensional and three-dimensional maps of genomes

Abstract

SummaryGenomes exist in vivo as complex physical structures, and their functional output (i.e. the gene expression profile of a cell) is related to their spatial organization inside the nucleus as well as to local chromatin status. Chromatin modifications and chromosome conformation are distinct in different tissues and cell types, which corresponds closely with the diversity in gene-expression patterns found in different tissues of the body. The biological processes and mechanisms driving these general correlations are currently the topic of intense study. An emerging theme is that genome compartmentalization -both along the linear length of chromosomes, and in three dimensions by the spatial colocalization of chromatin domains and genomic loci from across the genome -is a crucial parameter in regulating genome expression. In this Commentary, we propose that a full understanding of genome regulation requires integrating three different types of data: first, one-dimensional data regarding the state of local chromatin -such as patterns of protein binding along chromosomes; second, three-dimensional data that describe the population-averaged folding of chromatin inside cells and; third, single-cell observations of three-dimensional spatial colocalization of genetic loci and trans factors that reveal information about their dynamics and frequency of colocalization.This article is part of a Minifocus on exploring the nucleus. For further reading, please see related articles: 'The nuclear envelope at a glance' by Katherine L. Wilson and Jason M. Berk (J. Cell Sci. 123, 1973-1978 and 'Connecting the transcription site to the nuclear pore: a multi-tether process regulating gene expression' by Guennaëlle Dieppois and Françoise Stutz (J. Cell Sci. 123, 1989.

p63 and Brg1 control developmentally regulated higher-order chromatin remodelling at the epidermal differentiation complex locus in epidermal progenitor cells

“…Lineage-specific programmes of gene expression are characterised by distinct patterns of gene activation and silencing and are regulated at several levels, including the epigenetic control of chromatin structural states (Rando and Chang, 2009;Wang et al, 2009). Epigenetic regulatory mechanisms control covalent DNA and histone modifications, ATP-dependent chromatin remodelling, higher-order chromatin folding and the specific arrangement of genes and distinct chromatin domains within threedimensional (3D) nuclear space (Hubner et al, 2012;Naumova and Dekker, 2010;Rando and Chang, 2009;Wang et al, 2009).…”

Comparing Enhancer Action in Cis and in Trans

“…However, extensive analyses based on DNA fluorescence in situ hybridization (DNA FISH) and chromatin conformation capture (3C) have shown that the threedimensional organization of the nucleus involves physical interactions between distant genomic regions, suggesting that gene regulation is more complex than this simplified model (reviewed by Gondor and Ohlsson 2009;Naumova and Dekker 2010). Further complicating our view, long-distance interactions are not limited to genomic regions on the same chromosomes (in cis), but are also observed between specific loci on separate chromosomes (in trans) (reviewed by Williams et al 2010).…”

Structure determination of genomic domains by satisfaction of spatial restraints

“…Current methods, such as the worm-like chain model, among others (Langowski and Heermann 2007), have proven valuable for understanding general features of chromatin fibers, including flexi- Length, volume and resolution scales adapted from (Langowski and Heermann, 2007). Refer to (Naumova and Dekker, 2010) for a recent review on experimental 3D and 1D technologies.…”