Chromatin loops, gene positioning, and gene expression

Holwerda, Sjoerd J B; Laat, Wouter de

doi:10.3389/fgene.2012.00217

“…CTCF and cohesins have been implicated in DNA loop interactions (22,54,55). Long-distance DNA interactions are essential to mediate communication between promoter and enhancer regulatory elements.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Deregulation of the LMP1/LMP2 Locus of Epstein-Barr Virus by Mutation of a Single CTCF-Cohesin Binding Site

Chen

¹

,

Martin

²

,

Lü

³

et al. 2014

J Virol

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The chromatin regulatory factors CTCF and cohesin have been implicated in the coordinated control of multiple gene loci in Epstein-Barr virus (EBV) latency. We have found that CTCF and cohesin are highly enriched at the convergent and partially overlapping transcripts for the LMP1 and LMP2A genes, but it is not yet known how CTCF and cohesin may coordinately regulate these transcripts. We now show that genetic disruption of this CTCF binding site (EBV⌬CTCF166) leads to a deregulation of LMP1, LMP2A, and LMP2B transcription in EBV-immortalized B lymphocytes. EBV⌬CTCF166 virus-immortalized primary B lymphocytes showed a decrease in LMP1 and LMP2A mRNA and a corresponding increase in LMP2B mRNA. The reduction of LMP1 and LMP2A correlated with a loss of euchromatic histone modification H3K9ac and a corresponding increase in heterochromatic histone modification H3K9me3 at the LMP2A promoter region in EBV⌬CTCF166. Chromosome conformation capture (3C) revealed that DNA loop formation with the origin of plasmid replication (OriP) enhancer was eliminated in EBV⌬CTCF166. We also observed that the EBV episome copy number was elevated in EBV⌬CTCF166 and that this was not due to increased lytic cycle activity. These findings suggest that a single CTCF binding site controls LMP2A and LMP1 promoter selection, chromatin boundary function, DNA loop formation, and episome copy number control during EBV latency.

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“…A number of chromatin proteins, transcription factors and cofactors have been reported to participate in chromatin looping in different genomic contexts (Holwerda and de Laat, 2012). In this regard, the CCCTC-binding factor (CTCF) is the best characterized organizer of chromatin architecture.…”

Section: Introductionmentioning

confidence: 99%

Functional interplay between MyoD and CTCF in regulating long-range chromatin interactions during differentiation

Battistelli

¹

,

Busanello

²

,

Maione

³

2014

Journal of Cell Science

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BSTRACTHigher-order chromatin structures appear to be dynamically arranged during development and differentiation. However, the molecular mechanism underlying their maintenance or disruption and their functional relevance to gene regulation are poorly understood. We recently described a dynamic long-range chromatin interaction between the gene promoter of the cdk inhibitor p57 kip2 (also known as Cdkn1c) and the imprinting control region KvDMR1 in muscle cells. Here, we show that CTCF, the best characterized organizer of long-range chromatin interactions, binds to both the p57 kip2 promoter and KvDMR1 and is necessary for the maintenance of their physical contact. Moreover, we show that CTCF-mediated looping is required to prevent p57 kip2 expression before differentiation. Finally, we provide evidence that the induction of p57 kip2 during myogenesis involves the physical interaction of the muscle-regulatory factor MyoD with CTCF at KvDMR1, the displacement of the cohesin complex subunit Rad21 and the destabilization of the chromatin loop. The finding that MyoD affects chromatin looping at CTCF-binding sites represents the first evidence that a differentiation factor regulates chromatin-loop dynamics and provides a useful paradigm for gaining insights into the developmental regulation of long-range chromatin contacts.

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“…Dynamic changes of higher-order chromatin structures have been described for specific loci during developmental processes (Holwerda and de Laat, 2012;Misteli, 2007). However, little is known about the signalling pathways and the regulatory factors that functionally interact with chromatin complexes involved in the formation and/or maintenance of chromatin loops.…”

Section: Introductionmentioning

confidence: 99%

Functional interplay between MyoD and CTCF in regulating long-range chromatin interactions during differentiation

Battistelli¹,

Busanello²,

Maione³

2014

View full text Add to dashboard Cite

BSTRACTHigher-order chromatin structures appear to be dynamically arranged during development and differentiation. However, the molecular mechanism underlying their maintenance or disruption and their functional relevance to gene regulation are poorly understood. We recently described a dynamic long-range chromatin interaction between the gene promoter of the cdk inhibitor p57 kip2 (also known as Cdkn1c) and the imprinting control region KvDMR1 in muscle cells. Here, we show that CTCF, the best characterized organizer of long-range chromatin interactions, binds to both the p57 kip2 promoter and KvDMR1 and is necessary for the maintenance of their physical contact. Moreover, we show that CTCF-mediated looping is required to prevent p57 kip2 expression before differentiation. Finally, we provide evidence that the induction of p57 kip2 during myogenesis involves the physical interaction of the muscle-regulatory factor MyoD with CTCF at KvDMR1, the displacement of the cohesin complex subunit Rad21 and the destabilization of the chromatin loop. The finding that MyoD affects chromatin looping at CTCF-binding sites represents the first evidence that a differentiation factor regulates chromatin-loop dynamics and provides a useful paradigm for gaining insights into the developmental regulation of long-range chromatin contacts.

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Chromatin loops, gene positioning, and gene expression

Cited by 89 publications

References 140 publications

Epigenetic Deregulation of the LMP1/LMP2 Locus of Epstein-Barr Virus by Mutation of a Single CTCF-Cohesin Binding Site

Epigenetic Deregulation of the LMP1/LMP2 Locus of Epstein-Barr Virus by Mutation of a Single CTCF-Cohesin Binding Site

Functional interplay between MyoD and CTCF in regulating long-range chromatin interactions during differentiation

Functional interplay between MyoD and CTCF in regulating long-range chromatin interactions during differentiation

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