scholarly journals Boundaries mediate long-distance interactions between enhancers and promoters in the Drosophila Bithorax complex

PLoS Genetics ◽  
2018 ◽  
Vol 14 (12) ◽  
pp. e1007702 ◽  
Author(s):  
Nikolay Postika ◽  
Mario Metzler ◽  
Markus Affolter ◽  
Martin Müller ◽  
Paul Schedl ◽  
...  
2018 ◽  
Author(s):  
Nikolay Postika ◽  
Mario Metzler ◽  
Markus Affolter ◽  
Martin Müller ◽  
Paul Schedl ◽  
...  

AbstractDrosophila bithorax complex (BX-C) is one of the best model systems for studying the role of boundaries (insulators) in gene regulation. Expression of three homeotic genes, Ubx, abd-A, and Abd-B, is orchestrated by nine parasegment-specific regulatory domains. These domains are flanked by boundary elements, which function to block crosstalk between adjacent domains, ensuring that they can act autonomously. Paradoxically, seven of the BX-C regulatory domains are separated from their gene target by at least one boundary, and must “jump over” the intervening boundaries. To understand the jumping mechanism, the Mcp boundary was replaced with Fab-7 and Fab-8. Mcp is located between the iab-4 and iab-5 domains, and defines the border between the set of regulatory domains controlling abd-A and Abd-B. When Mcp is replaced by Fab-7 or Fab-8, they direct the iab-4 domain (which regulates abd-A) to inappropriately activate Abd-B in abdominal segment A4. For the Fab-8 replacement, ectopic induction was only observed when it was inserted in the same orientation as the endogenous Fab-8 boundary. A similar orientation dependence for bypass activity was observed when Fab-7 was replaced by Fab-8. Thus, boundaries perform two opposite functions in the context of BX-C – they block crosstalk between neighboring regulatory domains, but at the same time actively facilitate long distance communication between the regulatory domains and their respective target genes.Author SummaryDrosophila bithorax complex (BX-C) is one of a few examples demonstrating in vivo role of boundary/insulator elements in organization of independent chromatin domains. BX-C contains three HOX genes, whose parasegment-specific pattern is controlled by cis-regulatory domains flanked by boundary/insulator elements. Since the boundaries ensure autonomy of adjacent domains, the presence of these elements poses a paradox: how do the domains bypass the intervening boundaries and contact their proper regulatory targets? According to the textbook model, BX-C regulatory domains are able to bypass boundaries because they harbor special promoter targeting sequences. However, contrary to this model, we show here that the boundaries themselves play an active role in directing regulatory domains to their appropriate HOX gene promoter.


2019 ◽  
Vol 116 (27) ◽  
pp. 13462-13467 ◽  
Author(s):  
Olga Kyrchanova ◽  
Marat Sabirov ◽  
Vladic Mogila ◽  
Amina Kurbidaeva ◽  
Nikolay Postika ◽  
...  

Boundaries in the bithorax complex (BX-C) delimit autonomous regulatory domains that drive parasegment-specific expression of the Hox genes Ubx, abd-A, and Abd-B. The Fab-7 boundary is located between the iab-6 and iab-7 domains and has two key functions: blocking cross-talk between these domains and at the same time promoting communication (boundary bypass) between iab-6 and the Abd-B promoter. Using a replacement strategy, we found that multimerized binding sites for the architectural proteins Pita, Su(Hw), and dCTCF function as conventional insulators and block cross-talk between the iab-6 and iab-7 domains; however, they lack bypass activity, and iab-6 is unable to regulate Abd-B. Here we show that an ∼200-bp sequence of dHS1 from the Fab-7 boundary rescues the bypass defects of these multimerized binding sites. The dHS1 sequence is bound in embryos by a large multiprotein complex, Late Boundary Complex (LBC), that contains the zinc finger proteins CLAMP and GAF. Using deletions and mutations in critical GAGAG motifs, we show that bypass activity correlates with the efficiency of recruitment of LBC components CLAMP and GAF to the artificial boundary. These results indicate that LBC orchestrates long-distance communication between the iab-6 regulatory domain and the Abd-B gene, while the Pita, Su(Hw), and dCTCF proteins function to block local cross-talk between the neighboring regulatory domains iab-6 and iab-7.


Genetics ◽  
1999 ◽  
Vol 153 (3) ◽  
pp. 1333-1356 ◽  
Author(s):  
Martin Muller ◽  
Kirsten Hagstrom ◽  
Henrik Gyurkovics ◽  
Vincenzo Pirrotta ◽  
Paul Schedl

Abstract In the studies reported here, we have examined the properties of the Mcp element from the Drosophila melanogaster bithorax complex (BX-C). We have found that sequences from the Mcp region of BX-C have properties characteristic of Polycomb response elements (PREs), and that they silence adjacent reporters by a mechanism that requires trans-interactions between two copies of the transgene. However, Mcp trans-regulatory interactions have several novel features. In contrast to classical transvection, homolog pairing does not seem to be required. Thus, trans-regulatory interactions can be observed not only between Mcp transgenes inserted at the same site, but also between Mcp transgenes inserted at distant sites on the same chromosomal arm, or even on different arms. Trans-regulation can even be observed between transgenes inserted on different chromosomes. A small 800-bp Mcp sequence is sufficient to mediate these long-distance trans-regulatory interactions. This small fragment has little silencing activity on its own and must be combined with other Polycomb-Group-responsive elements to function as a “pairing-sensitive” silencer. Finally, this pairing element can also mediate long-distance interactions between enhancers and promoters, activating mini-white expression.


2006 ◽  
Vol 38 (8) ◽  
pp. 931-935 ◽  
Author(s):  
Fabienne Cléard ◽  
Yuri Moshkin ◽  
François Karch ◽  
Robert K Maeda

Author(s):  
James Cronshaw

Long distance transport in plants takes place in phloem tissue which has characteristic cells, the sieve elements. At maturity these cells have sieve areas in their end walls with specialized perforations. They are associated with companion cells, parenchyma cells, and in some species, with transfer cells. The protoplast of the functioning sieve element contains a high concentration of sugar, and consequently a high hydrostatic pressure, which makes it extremely difficult to fix mature sieve elements for electron microscopical observation without the formation of surge artifacts. Despite many structural studies which have attempted to prevent surge artifacts, several features of mature sieve elements, such as the distribution of P-protein and the nature of the contents of the sieve area pores, remain controversial.


VASA ◽  
2012 ◽  
Vol 41 (4) ◽  
pp. 262-268 ◽  
Author(s):  
Schweizer ◽  
Hügli ◽  
Koella ◽  
Jeanneret

On the occasion of diagnosing a popliteal entrapment syndrome in a 59-year old man with no cardiovascular risk factors, who developed acute ischemic leg pain during long distance running, we give an overview on this entity with emphasis on patients’age. The different types of the popliteal artery compression syndrome are summarized. The diagnostic and therapeutic approaches are discussed. The most important clinical sign of a popliteal entrapment syndrome is the lack of atherosclerotic risk factors in patients with limited walking distance. Not only in young athletes but also in patients more than 50 years old the popliteal entrapment syndrome has to be taken into account.


Sign in / Sign up

Export Citation Format

Share Document