scholarly journals Identification and Analysis of a Conserved Tcfap2a Intronic Enhancer Element Required for Expression in Facial and Limb Bud Mesenchyme

2007 ◽  
Vol 28 (1) ◽  
pp. 315-325 ◽  
Author(s):  
Weiguo Feng ◽  
Jian Huang ◽  
Jian Zhang ◽  
Trevor Williams

ABSTRACT Tcfap2a, the gene encoding the mouse AP-2α transcription factor, is required for normal development of multiple structures during embryogenesis, including the face and limbs. Using comparative sequence analysis and transgenic-mouse experiments we have identified an intronic enhancer within this gene that directs expression to the face and limb mesenchyme. There are two conserved sequence blocks within this intron, and the larger of these directs tissue-specific activity and is found in all vertebrate Tcfap2a genes analyzed. To assess the role of the enhancer in regulating endogenous mouse Tcfap2a expression, we have deleted this cis-regulatory sequence from the genome. Loss of this element severely impairs Tcfap2a expression in the limb bud mesenchyme but generates only a modest reduction in the facial mesenchyme. The reduction in Tcfap2a transcription is accompanied by altered patterning of the forelimb, resulting in postaxial polydactyly. These results indicate that the major role for this enhancer resides within the limb bud, and it serves to maintain a level of Tcfap2a expression that limits the size of the hand plate and the associated number of digit primordia. The potential role of this cis-acting sequence in modeling the size and shape of the face and limbs during evolution is discussed.

Microbiology ◽  
2005 ◽  
Vol 151 (11) ◽  
pp. 3723-3728 ◽  
Author(s):  
Meng Zhang ◽  
Kelly A. FitzGerald ◽  
Mary E. Lidstrom

A multiple A-tract sequence has been identified in the promoter regions for the mxaF, pqqA, mxaW, mxbD and mxcQ genes involved in methanol oxidation in Methylobacterium extorquens AM1, a facultative methylotroph. Site-directed mutagenesis was exploited to delete or change this conserved sequence. Promoter-xylE transcriptional fusions were used to assess promoter activity in these mutants. A fiftyfold drop in the XylE activity was observed for the mxaF and pqqA promoters without this sequence, and a five- to sixfold drop in the XylE activity was observed for the mxbD and mxcQ promoters without this sequence. Mutants were generated in the chromosomal copies in which this sequence was either deleted or altered, and these mutants were unable to grow on methanol. When one of these sequences was added to Plac of Escherichia coli, which is a weak constitutive promoter in M. extorquens AM1, the activity increased two- to threefold. These results suggest that this sequence is essential for normal expression of these genes in M. extorquens AM1, and may serve as a general enhancer element for genetic constructs in this bacterium.


2021 ◽  
Author(s):  
Jake Leyhr ◽  
Laura Waldmann ◽  
Beata Filipek-Górniok ◽  
Hanqing Zhang ◽  
Amin Allalou ◽  
...  

The acquisition of movable jaws was a major event during vertebrate evolution. The role of NK3 homeobox 2 (Nkx3.2) transcription factor in patterning the primary jaw joint of gnathostomes (jawed vertebrates) is well known, however knowledge about its regulatory mechanism is lacking. In this study, we report a proximal enhancer element of Nkx3.2 that is deeply conserved in gnathostomes but undetectable in the jawless hagfish. This enhancer is active in the developing jaw joint region of the zebrafish Danio rerio, and was thus designated as jaw joint regulatory sequence 1 (JRS1). We further show that JRS1 enhancer sequences from a range of gnathostome species, including a chondrichthyan and mammals, have the same activity in the jaw joint as the native zebrafish enhancer, indicating a high degree of functional conservation despite the divergence of cartilaginous and bony fish lineages or the transition of the primary jaw joint into the middle ear of mammals. Finally, we show that deletion of JRS1 from the zebrafish genome using CRISPR/Cas9 leads to a transient jaw joint deformation and partial fusion. Emergence of this Nkx3.2 enhancer in early gnathostomes may have contributed to the origin and shaping of the articulating surfaces of vertebrate jaws.


2002 ◽  
Vol 22 (12) ◽  
pp. 4293-4308 ◽  
Author(s):  
Charles K. Kaufman ◽  
Satrajit Sinha ◽  
Diana Bolotin ◽  
Jie Fan ◽  
Elaine Fuchs

ABSTRACT In this report, we explored the mechanisms underlying keratinocyte-specific and differentiation-specific gene expression in the skin. We have identified five keratinocyte-specific, open chromatin regions that exist within the 6 kb of 5′ upstream regulatory sequence known to faithfully recapitulate the strong endogenous keratin 5 (K5) promoter and/or enhancer activity. One of these, DNase I-hypersensitive site (HSs) 4, was unique in that it acted independently to drive abundant and keratinocyte-specific reporter gene activity in culture and in transgenic mice, despite the fact that it was not essential for K5 enhancer activity. We have identified evolutionarily conserved regulatory elements and a number of their associated proteins that bind to this compact and complex enhancer element. The 125-bp 3′ half of this element (referred to as 4.2) is by far the smallest known strong enhancer element possessing keratinocyte-specific activity in vivo. Interestingly, its activity is restricted to a subset of progeny of K5-expressing cells located within the sebaceous gland. The other half of HSs 4 (termed 4.1) possesses activity to suppress sebocyte-specific expression and induce expression in the channel (inner root sheath) cells surrounding the hair shaft. Our findings lead us to a view of keratinocyte gene expression which is determined by multiple regulatory modules, many of which contain AP-2 and/or Sp1/Sp3 binding sites for enhancing expression in skin epithelium, but which also harbor one or more unique sites for the binding of factors which determine specificity. Through mixing and matching of these modules, additional levels of specificity are obtained, indicating that both transcriptional repressors and activators govern the specificity.


2020 ◽  
Vol 99 (4) ◽  
pp. 379-383
Author(s):  
Vasily N. Afonyushkin ◽  
N. A. Donchenko ◽  
Ju. N. Kozlova ◽  
N. A. Davidova ◽  
V. Yu. Koptev ◽  
...  

Pseudomonas aeruginosa is a widely represented species of bacteria possessing of a pathogenic potential. This infectious agent is causing wound infections, fibrotic cystitis, fibrosing pneumonia, bacterial sepsis, etc. The microorganism is highly resistant to antiseptics, disinfectants, immune system responses of the body. The responses of a quorum sense of this kind of bacteria ensure the inclusion of many pathogenicity factors. The analysis of the scientific literature made it possible to formulate four questions concerning the role of biofilms for the adaptation of P. aeruginosa to adverse environmental factors: Is another person appears to be predominantly of a source an etiological agent or the source of P. aeruginosa infection in the environment? Does the formation of biofilms influence on the antibiotic resistance? How the antagonistic activity of microorganisms is realized in biofilm form? What is the main function of biofilms in the functioning of bacteria? A hypothesis has been put forward the effect of biofilms on the increase of antibiotic resistance of bacteria and, in particular, P. aeruginosa to be secondary in charcter. It is more likely a biofilmboth to fulfill the function of storing nutrients and provide topical competition in the face of food scarcity. In connection with the incompatibility of the molecular radii of most antibiotics and pores in biofilm, biofilm is doubtful to be capable of performing a barrier function for protecting against antibiotics. However, with respect to antibodies and immunocompetent cells, the barrier function is beyond doubt. The biofilm is more likely to fulfill the function of storing nutrients and providing topical competition in conditions of scarcity of food resources.


Author(s):  
Ronald Hoinski ◽  
Ronald Polansky

David Hoinski and Ronald Polansky’s “The Modern Aristotle: Michael Polanyi’s Search for Truth against Nihilism” shows how the general tendencies of contemporary philosophy of science disclose a return to the Aristotelian emphasis on both the formation of dispositions to know and the role of the mind in theoretical science. Focusing on a comparison of Michael Polanyi and Aristotle, Hoinski and Polansky investigate to what degree Aristotelian thought retains its purchase on reality in the face of the changes wrought by modern science. Polanyi’s approach relies on several Aristotelian assumptions, including the naturalness of the human desire to know, the institutional and personal basis for the accumulation of knowledge, and the endorsement of realism against objectivism. Hoinski and Polansky emphasize the promise of Polanyi’s neo-Aristotelian framework, which argues that science is won through reflection on reality.


2019 ◽  
Vol 3 (11) ◽  
pp. 1
Author(s):  
Harith Qahtan Abdullah ◽  
Abbas Fadel Atwan

The borders of Kurdistan represent an important point in Kurdish thought. They represent the hope of establishing their national state. The circumstances of the war on terrorism in Iraq and Syria have led to the emergence of what is known as a "propaganda" and the formation of a global front in its struggle. And with the signs of the collapse of the Syrian state and the weakness of the Iraqi state in the face of the "dashing" in the beginning. These circumstances led to the emergence of the role of the Kurdistan region in the confrontation "ISIS" and maintain the administrative border in the three provinces of Kurdistan in addition to the province of Kirkuk. That the circumstances of the war on terrorism created new international conditions on the Middle East arena, which will generate many problems between the Kurdistan region and the central government of Baghdad, as well as other problems between the region, Syria, Turkey and Iran. The war on terrorism has made countries free to fight the opposition groups under the name Terrorism by their classification. The Turkish side is fighting the PKK within the borders of the Kurdistan region, and this war can develop in a post-"warlike" phase. The war in Syria is also contradictory to vision and not resolved to a specific side and Iran's position on developments is encouraging.


2016 ◽  
Vol 1 (1) ◽  
pp. 45-57 ◽  
Author(s):  
Christina Landman

A majority of the black community of Dullstroom-Emnotweni in the Mpumalanga highveld in the east of South Africa trace their descent back to the southern Ndebele of the so-called ‘Mapoch Gronden’, who lost their land in the 1880s to become farm workers on their own land. A hundred years later, in 1980, descendants of the ‘Mapoggers’ settled in the newly built ‘township’ of Dullstroom, called Sakhelwe, finding jobs on the railways or as domestic workers. Oral interviews with the inhabitants of Sakhelwe – a name eventually abandoned in favour of Dullstroom- Emnotweni – testify to histories of transition from landowner to farmworker to unskilled labourer. The stories also highlight cultural conflicts between people of Ndebele, Pedi and Swazi descent and the influence of decades of subordination on local identities. Research projects conducted in this and the wider area of the eMakhazeni Local Municipality reveal the struggle to maintain religious, gender and youth identities in the face of competing political interests. Service delivery, higher education, space for women and the role of faith-based organisations in particular seem to be sites of contestation. Churches and their role in development and transformation, where they compete with political parties and state institutions, are the special focus of this study. They attempt to remain free from party politics, but are nevertheless co-opted into contra-culturing the lack of service delivery, poor standards of higher education and inadequate space for women, which are outside their traditional role of sustaining an oppressed community.


2018 ◽  
Vol 15 (2) ◽  
Author(s):  
Lufuluvhi Maria Mudimeli

This article is a reflection on the role and contribution of the church in a democratic South Africa. The involvement of the church in the struggle against apartheid is revisited briefly. The church has played a pivotal and prominent role in bringing about democracy by being a prophetic voice that could not be silenced even in the face of death. It is in this time of democracy when real transformation is needed to take its course in a realistic way, where the presence of the church has probably been latent and where it has assumed an observer status. A look is taken at the dilemmas facing the church. The church should not be bound and taken captive by any form of loyalty to any political organisation at the expense of the poor and the voiceless. A need for cooperation and partnership between the church and the state is crucial at this time. This paper strives to address the role of the church as a prophetic voice in a democratic South Africa. Radical economic transformation, inequality, corruption, and moral decadence—all these challenges hold the potential to thwart our young democracy and its ideals. Black liberation theology concepts are employed to explore how the church can become prophetically relevant in democracy. Suggestions are made about how the church and the state can best form partnerships. In avoiding taking only a critical stance, the church could fulfil its mandate “in season and out of season” and continue to be a prophetic voice on behalf of ordinary South Africans.


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