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Transcriptional Enhancers in the Regulation of T Cell Differentiation.

Nguyen ML, Jones SA, Prier JE, Russ BE - Front Immunol (2015)

Bottom Line: The changes in phenotype and function that characterize the differentiation of naïve T cells to effector and memory states are underscored by large-scale, coordinated, and stable changes in gene expression.Here, we focus on the mechanisms that control T cell differentiation, with a particular focus on the role of regulatory elements encoded within the genome, known as transcriptional enhancers (TEs).We discuss the central role of TEs in regulating T cell differentiation, both in health and disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne , Melbourne, VIC , Australia.

ABSTRACT
The changes in phenotype and function that characterize the differentiation of naïve T cells to effector and memory states are underscored by large-scale, coordinated, and stable changes in gene expression. In turn, these changes are choreographed by the interplay between transcription factors and epigenetic regulators that act to restructure the genome, ultimately ensuring lineage-appropriate gene expression. Here, we focus on the mechanisms that control T cell differentiation, with a particular focus on the role of regulatory elements encoded within the genome, known as transcriptional enhancers (TEs). We discuss the central role of TEs in regulating T cell differentiation, both in health and disease.

No MeSH data available.


Related in: MedlinePlus

The chromatin conformation capture (3C) assay. The 3C assay is used to measure chromatin loops that define promoter–enhancer interactions. Promoter–enhancer interactions are cross-linked, chromatin is then digested with a restriction enzyme, and the resulting restriction fragments are ligated under dilute conditions to favor the ligation of DNA fragments that are in close proximity due to being held together by cross-links. The resulting ligation products are then purified, subjected to quantitative PCR, or high-throughput sequencing (Hi-C).
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Figure 3: The chromatin conformation capture (3C) assay. The 3C assay is used to measure chromatin loops that define promoter–enhancer interactions. Promoter–enhancer interactions are cross-linked, chromatin is then digested with a restriction enzyme, and the resulting restriction fragments are ligated under dilute conditions to favor the ligation of DNA fragments that are in close proximity due to being held together by cross-links. The resulting ligation products are then purified, subjected to quantitative PCR, or high-throughput sequencing (Hi-C).

Mentions: Chromatin looping is measured using the chromatin conformation capture (3C) assay (Figure 3), and various adaptations to allow locus-wide and genome-wide measurement using high-throughput sequencing technologies (for instance, Hi-C) (49, 50). 3C involves cross-linking the protein–DNA and protein–protein interactions that characterize promoter–enhancer interactions. Cross-linked DNA is then digested with a restriction enzyme, and the resulting restriction fragments are ligated under conditions that favor intra rather than inter molecular ligation, thus allowing enhancers to be ligated to the promoters that they regulate (51). These ligation events can, then, be measured at individual loci by real-time PCR, or genome-wide using high-throughput sequencing.


Transcriptional Enhancers in the Regulation of T Cell Differentiation.

Nguyen ML, Jones SA, Prier JE, Russ BE - Front Immunol (2015)

The chromatin conformation capture (3C) assay. The 3C assay is used to measure chromatin loops that define promoter–enhancer interactions. Promoter–enhancer interactions are cross-linked, chromatin is then digested with a restriction enzyme, and the resulting restriction fragments are ligated under dilute conditions to favor the ligation of DNA fragments that are in close proximity due to being held together by cross-links. The resulting ligation products are then purified, subjected to quantitative PCR, or high-throughput sequencing (Hi-C).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4563239&req=5

Figure 3: The chromatin conformation capture (3C) assay. The 3C assay is used to measure chromatin loops that define promoter–enhancer interactions. Promoter–enhancer interactions are cross-linked, chromatin is then digested with a restriction enzyme, and the resulting restriction fragments are ligated under dilute conditions to favor the ligation of DNA fragments that are in close proximity due to being held together by cross-links. The resulting ligation products are then purified, subjected to quantitative PCR, or high-throughput sequencing (Hi-C).
Mentions: Chromatin looping is measured using the chromatin conformation capture (3C) assay (Figure 3), and various adaptations to allow locus-wide and genome-wide measurement using high-throughput sequencing technologies (for instance, Hi-C) (49, 50). 3C involves cross-linking the protein–DNA and protein–protein interactions that characterize promoter–enhancer interactions. Cross-linked DNA is then digested with a restriction enzyme, and the resulting restriction fragments are ligated under conditions that favor intra rather than inter molecular ligation, thus allowing enhancers to be ligated to the promoters that they regulate (51). These ligation events can, then, be measured at individual loci by real-time PCR, or genome-wide using high-throughput sequencing.

Bottom Line: The changes in phenotype and function that characterize the differentiation of naïve T cells to effector and memory states are underscored by large-scale, coordinated, and stable changes in gene expression.Here, we focus on the mechanisms that control T cell differentiation, with a particular focus on the role of regulatory elements encoded within the genome, known as transcriptional enhancers (TEs).We discuss the central role of TEs in regulating T cell differentiation, both in health and disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne , Melbourne, VIC , Australia.

ABSTRACT
The changes in phenotype and function that characterize the differentiation of naïve T cells to effector and memory states are underscored by large-scale, coordinated, and stable changes in gene expression. In turn, these changes are choreographed by the interplay between transcription factors and epigenetic regulators that act to restructure the genome, ultimately ensuring lineage-appropriate gene expression. Here, we focus on the mechanisms that control T cell differentiation, with a particular focus on the role of regulatory elements encoded within the genome, known as transcriptional enhancers (TEs). We discuss the central role of TEs in regulating T cell differentiation, both in health and disease.

No MeSH data available.


Related in: MedlinePlus