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Getting the genome in shape: the formation of loops, domains and compartments.

Bouwman BA, de Laat W - Genome Biol. (2015)

Bottom Line: The hierarchical levels of genome architecture exert transcriptional control by tuning the accessibility and proximity of genes and regulatory elements.Here, we review current insights into the trans-acting factors that enable the genome to flexibly adopt different functionally relevant conformations.

View Article: PubMed Central - PubMed

Affiliation: Hubrecht Institute - KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.

ABSTRACT
The hierarchical levels of genome architecture exert transcriptional control by tuning the accessibility and proximity of genes and regulatory elements. Here, we review current insights into the trans-acting factors that enable the genome to flexibly adopt different functionally relevant conformations.

No MeSH data available.


Different scenarios for cohesin-mediated chromatin looping. Three hypotheses for the strategy by which the cohesin complex is involved in the formation of chromatin loops. a After initial association of cohesin to one roadblock (such as CTCF), cohesin holds on to this site, and the flanking chromatin is pulled through until a second roadblock is encountered. b The cohesin ring remains open when the complex is attached to one roadblock. Only when a second cognate anchor sequence comes in close proximity does the ring close efficiently. c Cohesin embraces the DNA anchors of a loop that are already held together by other proteins (left-hand cartoons); its embrace stabilizes maintenance of the loops (right-hand cartoons)
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Fig3: Different scenarios for cohesin-mediated chromatin looping. Three hypotheses for the strategy by which the cohesin complex is involved in the formation of chromatin loops. a After initial association of cohesin to one roadblock (such as CTCF), cohesin holds on to this site, and the flanking chromatin is pulled through until a second roadblock is encountered. b The cohesin ring remains open when the complex is attached to one roadblock. Only when a second cognate anchor sequence comes in close proximity does the ring close efficiently. c Cohesin embraces the DNA anchors of a loop that are already held together by other proteins (left-hand cartoons); its embrace stabilizes maintenance of the loops (right-hand cartoons)

Mentions: Cohesin is a protein complex that forms a large ring-like structure to hold the sister chromatids together after DNA replication. In recent years, cohesin has also been found to bind to chromatin in post-mitotic cells [72–74]. Cohesin associates with chromatin at random locations and is thought to slide along the chromatin template. For stable positioning, cohesin relies on chromatin-bound factors, such as CTCF, which might serve as “roadblocks” when bound to chromatin [72]. Cohesin was indeed found to co-associate often at sites occupied by CTCF, but was in addition identified frequently at enhancer-promoter loops bound by the transcriptional coactivator known as mediator [67]. Cohesin might contribute to, or be responsible for, chromatin loops through its ability to embrace two double-stranded DNA helices, supporting an attractive model for cohesin in chromatin organization. How cohesin reaches and grabs the second defined anchor sequence of the to-be-established chromatin loop remains to be determined. One scenario involves a cohesin ring holding on to one associated factor or roadblock, while the flanking chromatin template is pulled through the ring until another roadblock is encountered (Fig. 3a). Alternatively, one can speculate that efficient closure of the cohesin ring only occurs when a cognate anchor sequence with associated factors comes into close physical proximity (Fig. 3b). A third possibility is that cohesin only associates after initial engagement, mediated by CTCF, mediator, and/or transcription factors, to embrace and further stabilize a long-range contact (Fig. 3c). In any of these scenarios, it would be interesting to find out whether cohesin adopts a preferred position upstream or downstream of the oriented CTCF binding site or other cohesin-recruiting roadblocks.Fig. 3


Getting the genome in shape: the formation of loops, domains and compartments.

Bouwman BA, de Laat W - Genome Biol. (2015)

Different scenarios for cohesin-mediated chromatin looping. Three hypotheses for the strategy by which the cohesin complex is involved in the formation of chromatin loops. a After initial association of cohesin to one roadblock (such as CTCF), cohesin holds on to this site, and the flanking chromatin is pulled through until a second roadblock is encountered. b The cohesin ring remains open when the complex is attached to one roadblock. Only when a second cognate anchor sequence comes in close proximity does the ring close efficiently. c Cohesin embraces the DNA anchors of a loop that are already held together by other proteins (left-hand cartoons); its embrace stabilizes maintenance of the loops (right-hand cartoons)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4536798&req=5

Fig3: Different scenarios for cohesin-mediated chromatin looping. Three hypotheses for the strategy by which the cohesin complex is involved in the formation of chromatin loops. a After initial association of cohesin to one roadblock (such as CTCF), cohesin holds on to this site, and the flanking chromatin is pulled through until a second roadblock is encountered. b The cohesin ring remains open when the complex is attached to one roadblock. Only when a second cognate anchor sequence comes in close proximity does the ring close efficiently. c Cohesin embraces the DNA anchors of a loop that are already held together by other proteins (left-hand cartoons); its embrace stabilizes maintenance of the loops (right-hand cartoons)
Mentions: Cohesin is a protein complex that forms a large ring-like structure to hold the sister chromatids together after DNA replication. In recent years, cohesin has also been found to bind to chromatin in post-mitotic cells [72–74]. Cohesin associates with chromatin at random locations and is thought to slide along the chromatin template. For stable positioning, cohesin relies on chromatin-bound factors, such as CTCF, which might serve as “roadblocks” when bound to chromatin [72]. Cohesin was indeed found to co-associate often at sites occupied by CTCF, but was in addition identified frequently at enhancer-promoter loops bound by the transcriptional coactivator known as mediator [67]. Cohesin might contribute to, or be responsible for, chromatin loops through its ability to embrace two double-stranded DNA helices, supporting an attractive model for cohesin in chromatin organization. How cohesin reaches and grabs the second defined anchor sequence of the to-be-established chromatin loop remains to be determined. One scenario involves a cohesin ring holding on to one associated factor or roadblock, while the flanking chromatin template is pulled through the ring until another roadblock is encountered (Fig. 3a). Alternatively, one can speculate that efficient closure of the cohesin ring only occurs when a cognate anchor sequence with associated factors comes into close physical proximity (Fig. 3b). A third possibility is that cohesin only associates after initial engagement, mediated by CTCF, mediator, and/or transcription factors, to embrace and further stabilize a long-range contact (Fig. 3c). In any of these scenarios, it would be interesting to find out whether cohesin adopts a preferred position upstream or downstream of the oriented CTCF binding site or other cohesin-recruiting roadblocks.Fig. 3

Bottom Line: The hierarchical levels of genome architecture exert transcriptional control by tuning the accessibility and proximity of genes and regulatory elements.Here, we review current insights into the trans-acting factors that enable the genome to flexibly adopt different functionally relevant conformations.

View Article: PubMed Central - PubMed

Affiliation: Hubrecht Institute - KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.

ABSTRACT
The hierarchical levels of genome architecture exert transcriptional control by tuning the accessibility and proximity of genes and regulatory elements. Here, we review current insights into the trans-acting factors that enable the genome to flexibly adopt different functionally relevant conformations.

No MeSH data available.