Gene expression in time and space: additive vs hierarchical organization of cis-regulatory regions

Maeda, Robert K.; Karch, François

doi:10.1016/j.gde.2011.01.021

Cited by 29 publications

(25 citation statements)

References 56 publications

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“…36, 38 Here we have found that ENY2 interacts with dCTCF and is required for blocking PRE-mediated repression by the Fab-8 and Mcp boundaries in transgenic lines. Thus, our results confirm that dCTCFdependent insulators can protect gene expression from PcG repression and that the recruitment of ENY2 by dCTCF is essential for this process.…”

Section: Discussionmentioning

confidence: 77%

“…[32][33][34][35] One of the best model systems for studying the role of insulators in gene regulation is the regulatory region of the homeotic Abdominal-B (Abd-B) gene of the bithorax complex. 36,37 The large cis-regulatory region of the bithorax complex (BX-C) is divided into nine parasegment-specific chromatin domains that control the expression of the three homeotic genes, Ultrabithorax (Ubx), Abdominal-A (Abd-A), and Abdominal-B (Abd-B). 38 These genes are responsible for specifying the identity of parasegments 5 to 14 (PS5-PS14), which form the posterior half of the thorax and all abdominal segments of an adult fly.…”

Section: Introductionmentioning

confidence: 99%

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Highly conserved ENY2/Sus1 protein binds toDrosophilaCTCF and is required for barrier activity

et al. 2014

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Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Highly conserved ENY2/Sus1 protein binds toDrosophilaCTCF and is required for barrier activity

et al. 2014

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“…All the regulatory domains in the BX-C appear to share a similar set of individual regulatory elements (Maeda and Karch, 2011, 2009, 2006). Each domain has an “initiator” element (* in Figure 1B) that is responsible for establishing its activity state, either on or off .…”

Section: Regulatory Elements In the Bithorax Complexmentioning

confidence: 99%

The boundary paradox in the Bithorax complex

Kyrchanova

Mogila

Wolle

et al. 2015

Mechanisms of Development

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The parasegment-specific expression of the three Drosophila Bithorax complex homeotic genes is orchestrated by nine functionally autonomous regulatory domains. Functional autonomy depends upon special elements called boundaries or insulators that are located between each domain. The boundaries ensure the independent activity of each domain by blocking adventitious interactions with initiators, enhancers and silencers in the neighboring domains. However, this blocking activity poses a regulatory paradox--the Bithorax boundaries are also able to insulate promoters from regulatory interactions with enhancers and silencers and six of the nine Bithorax regulatory domains are separated from their target genes by at least one boundary element. Here we consider several mechanisms that have been suggested for how the Bithorax regulatory domains are able to bypass intervening boundary elements and direct the appropriate parasegment-specific temporal and spatial expression of their target gene.

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“…Such ‘long-range interactions’ have been first observed between promoters and distant enhancers ([3,4] and references therein) and can bring DNA elements together that are separated by a large distance on the linear DNA strand ([5,6] and references therein). These regulatory elements (enhancers or silencers) are short sequences containing several binding sites for transcription factors, which regulate the activation (reviewed in [7]) repression (reviewed in [8]) genes and their subsequent transcription (reviewed in [9]). In the linear genome the distance between enhancer(s) and gene can be quite large, for example, the sonic hedgehog (shh) enhancer is located about 1 Mb away from its target gene Shh [10].…”

Section: Introductionmentioning

confidence: 99%

Targeted Chromatin Capture (T2C): a novel high resolution high throughput method to detect genomic interactions and regulatory elements

Kolovos

Werken

Kepper

et al. 2014

Epigenetics & Chromatin

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BackgroundSignificant efforts have recently been put into the investigation of the spatial organization and the chromatin-interaction networks of genomes. Chromosome conformation capture (3C) technology and its derivatives are important tools used in this effort. However, many of these have limitations, such as being limited to one viewpoint, expensive with moderate to low resolution, and/or requiring a large sequencing effort. Techniques like Hi-C provide a genome-wide analysis. However, it requires massive sequencing effort with considerable costs. Here we describe a new technique termed Targeted Chromatin Capture (T2C), to interrogate large selected regions of the genome. T2C provides an unbiased view of the spatial organization of selected loci at superior resolution (single restriction fragment resolution, from 2 to 6 kbp) at much lower costs than Hi-C due to the lower sequencing effort.ResultsWe applied T2C on well-known model regions, the mouse β-globin locus and the human H19/IGF2 locus. In both cases we identified all known chromatin interactions. Furthermore, we compared the human H19/IGF2 locus data obtained from different chromatin conformation capturing methods with T2C data. We observed the same compartmentalization of the locus, but at a much higher resolution (single restriction fragments vs. the common 40 kbp bins) and higher coverage. Moreover, we compared the β-globin locus in two different biological samples (mouse primary erythroid cells and mouse fetal brain), where it is either actively transcribed or not, to identify possible transcriptional dependent interactions. We identified the known interactions in the β-globin locus and the same topological domains in both mouse primary erythroid cells and in mouse fetal brain with the latter having fewer interactions probably due to the inactivity of the locus. Furthermore, we show that interactions due to the important chromatin proteins, Ldb1 and Ctcf, in both tissues can be analyzed easily to reveal their role on transcriptional interactions and genome folding.ConclusionsT2C is an efficient, easy, and affordable with high (restriction fragment) resolution tool to address both genome compartmentalization and chromatin-interaction networks for specific genomic regions at high resolution for both clinical and non-clinical research.

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Gene expression in time and space: additive vs hierarchical organization of cis-regulatory regions

Cited by 29 publications

References 56 publications

Highly conserved ENY2/Sus1 protein binds toDrosophilaCTCF and is required for barrier activity

Highly conserved ENY2/Sus1 protein binds toDrosophilaCTCF and is required for barrier activity

The boundary paradox in the Bithorax complex

Targeted Chromatin Capture (T2C): a novel high resolution high throughput method to detect genomic interactions and regulatory elements

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