Home
This Title All WIREs
WIREs RSS Feed
How to cite this WIREs title:
WIREs Dev Biol
Impact Factor: 3.754

Chromatin looping and organization at developmentally regulated gene loci

Full article on Wiley Online Library:   HTML PDF

Can't access this content? Tell your librarian.

Abstract Developmentally regulated genes are often controlled by distant enhancers, silencers and insulators, to implement their correct transcriptional programs. In recent years, the development of 3C and derived techniques (4C, 5C, HiC, ChIA‐PET, etc.) has confirmed that chromatin looping is an important mechanism for the transfer of regulatory information in mammalian cells. At many developmentally regulated gene loci, transcriptional activation is indeed accompanied by the formation of chromatin loops between genes and distant enhancers. Similarly, dynamic looping between insulator elements and changes in local 3D organization may be observed upon variation in transcriptional activity. Chromatin looping also occurs at silent gene loci, where its function remains less understood. In lineage‐committed cells, partial 3D configurations are detected at loci that are activated at later stages. However, these partial configurations usually lack promoter–enhancer loops that accompany transcriptional activation, suggesting they have structural functions. Definitive evidence for a repressive role of chromatin looping is still lacking. Chromatin loops have been reported at repressed loci but, alternatively, they may act as a distraction for active loops. Together, these mechanisms allow fine‐tuning of regulatory programs, thus providing further diversity in the transcriptional control of developmentally regulated gene loci. WIREs Dev Biol 2013, 2:615–630. doi: 10.1002/wdev.103 This article is categorized under: Gene Expression and Transcriptional Hierarchies > Regulatory Mechanisms

This WIREs title offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Chromosome Conformation Capture (3C) and derivatives. (a) Schematic overview of the experimental procedure for 3C and techniques derived thereof. Top: common steps to generate a 3C library. Middle: specific steps for each variant. Bottom: strategies for read out. (b) Illustration of the differences between direct, physical interactions and stepwise, functional interactions. Fragments that are directly cross‐linked (top) or that share protein complexes (bottom) may both be ligated together. Cross‐links are indicated as black stripes and proteins as grey ovals. (c) Matrix showing the number of viewpoints and the interrogated interaction partners for variants of the 3C technique.

[ Normal View | Magnified View ]

3D chromatin organization of mammalian Hox loci. (a) Genomic organization of the mouse HoxD cluster and genomic environment. Top: the HoxD cluster is flanked by two gene deserts. The HoxD cluster is indicated in red, other genes in grey and the location of regulatory regions in developing digits is indicated by black stars. Bottom: enlargement of the HoxD cluster, with individual Hoxd genes indicated in red. (b) Expression pattern of Hoxd genes in developing digits. Absolute expression levels are provided relative to Hoxd13 levels. Panel compiled from data presented in Ref. . Copyright 2008 Cold Spring Harbor Laboratory Press. (c) Schematic illustration of long‐range chromatin looping at the HoxD cluster in developing digits (left) and non‐expressing brain cells (right). (d) Local 3D organization of the mouse HoxD cluster in inactive mouse brain cells. 4C signal with viewpoints Hoxd13 and Hoxd4 (grey bars) displays the same borders as the repressive H3K27me3 ChIP‐seq signal. Inactive genes are indicated in red. Panel compiled from data presented in Ref. . Copyright 2011 American Association for the Advancement of Science. (e) Local 3D organization of the mouse HoxD cluster in cells along the primary AP‐axis where Hoxd gene activity is detected up to Hoxd8. The 4C signal with the inactive Hoxd13 viewpoint displays the same borders as the repressive H3K27me3 ChIP‐seq signal, whereas the 4C signal with the active Hoxd4 viewpoint displays the same borders as the active H3K4me3 ChIP‐seq signal. Inactive genes are indicated in red and active genes in blue. Panel compiled from data presented in Ref. . Copyright 2011 American Association for the Advancement of Science. (f) Schematic representation of the dynamic 3D organization of the mouse HoxD cluster along the primary AP‐axis. Inactive genes are indicated in red and active genes in blue. Top: In inactive brain cells, the HoxD cluster is organized as a single 3D compartment that separates the H3K27me3 marked chromatin from its surroundings. Bottom: the partially activated HoxD cluster along the AP‐axis adopts a bimodal organization, separating active and inactive chromatin from each other, as well as from their surroundings.

[ Normal View | Magnified View ]

Examples of 3D chromatin organization in mammals. (a) Active chromatin loops at the mouse TH2 locus. Genomic organization is depicted on the left, schematic representation of 3D organization in nonexpressing cell in the middle, and in actively expressing cells at the right. The interleukin genes are indicated by red boxes and the Rad50 gene, which is not involved in chromatin looping by a light grey box. Hypersensitive sites in the LCR are indicated by black arrowheads. (b) Active, very long‐range chromatin loops at the mouse Shh locus. The genomic organization is shown on the left, whereas a schematic representation of 3D organization in the subpopulation of actively expressing cells is depicted on the right. The Shh gene is indicated by a red box, other genes by light grey boxes and enhancers by black stars. (c) Structural chromatin loops at the human MHC I cluster. The genomic organization is on the left and the schematic representation of 3D organization in moderately expressing Jurkat cells is shown on the right. Genes are indicated by light grey boxes and the shaded surface represents the surface of the nuclear matrix/PML bodies. (d) Alternative silent and active loops at the mouse Dlx5/Dlx6 locus. The genomic organization is shown on the left, the schematic representation of 3D organization in non‐expressing WT cells depicted in the middle and the situation in expressing MBD2 mutant cells is on the right. The Dlx5 gene is indicated by a red box, other genes by light grey boxes, enhancers by black stars and the MECP2 binding site by a black oval. (e) Alternative active and silent loops at the mouse Kit locus. The genomic organization is shown on the left, a schematic representation of the 3D organization in expressing erythtroid progenitor cells is depicted in the middle and the situation in nonexpressing mature erythroid cells is illustrated on the right. The Kit gene is indicated by a red box and GATA‐2/GATA‐1 binding sites by black ovals. (f) Alternative looping at the mouse Igf2/H19 locus. The genomic organization is shown on the left, a schematic representation of the 3D organization in maternal H19 expression cells is depicted in the middle and the situation in the paternal Igf2 expressing cells is illustrated on the right. Genes are indicated by red boxes, the enhancer by a black star whereas DMRs are indicated with black diamonds.

[ Normal View | Magnified View ]

Chromatin looping at the mammalian globin loci. (a) Genomic organization of the mouse and human β‐globin loci. (b) Schematic 2D illustration of 3D chromatin organization at the mouse β‐globin locus in nonexpressing brain cells (left), nonexpressing erythroid progenitor cells (middle) and fetal/adult erythroid cells expressing the βmaj and βmin genes (right). (c) Genomic organization of the mouse and human α‐globin loci. (d) Schematic 2D illustration of 3D chromatin organization at the mouse α‐globin locus in α1 and α2 expressing fetal erythroid cells and induced MEL cells. Globin genes are indicated by red block arrows, other genes by light grey boxes and hypersensitive sites by black arrowheads.

[ Normal View | Magnified View ]

Browse by Topic

Gene Expression and Transcriptional Hierarchies > Regulatory Mechanisms