scholarly journals An evolutionarily conserved cis-regulatory element of Nkx3.2 contributes to early jaw joint morphology in zebrafish

2021 ◽  
Author(s):  
Jake Leyhr ◽  
Laura Waldmann ◽  
Beata Filipek-Górniok ◽  
Hanqing Zhang ◽  
Amin Allalou ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Regulatory Sequence ◽  
Enhancer Element ◽  
Functional Conservation ◽  
Evolutionarily Conserved ◽  
Joint Deformation ◽  
Jaw Joint ◽  
Enhancer Sequences ◽  
High Degree

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.

Identification of an evolutionarily conserved 110 base-pair cis-acting regulatory sequence that governs Wnt-1 expression in the murine neural plate

Development ◽  
1998 ◽  
Vol 125 (14) ◽  
pp. 2735-2746 ◽  
Author(s):  
D.H. Rowitch ◽  
Y. Echelard ◽  
P.S. Danielian ◽  
K. Gellner ◽  
S. Brenner ◽  
...  
Keyword(s):  
Base Pair ◽  
Regulatory Element ◽  
Regulatory Region ◽  
Neural Plate ◽  
Homologous Region ◽  
Regulatory Sequence ◽  
Embryonic Mouse ◽  
Cis Acting ◽  
Evolutionarily Conserved

The generation of anterior-posterior polarity in the vertebrate brain requires the establishment of regional domains of gene expression at early somite stages. Wnt-1 encodes a signal that is expressed in the developing midbrain and is essential for midbrain and anterior hindbrain development. Previous work identified a 5.5 kilobase region located downstream of the Wnt-1 coding sequence which is necessary and sufficient for Wnt-1 expression in vivo. Using a transgenic mouse reporter assay, we have now identified a 110 base pair regulatory sequence within the 5.5 kilobase enhancer, which is sufficient for expression of a lacZ reporter in the approximate Wnt-1 pattern at neural plate stages. Multimers of this element driving Wnt-1 expression can partially rescue the midbrain-hindbrain phenotype of Wnt-1(−/−) embryos. The possibility that this region represents an evolutionarily conserved regulatory module is suggested by the identification of a highly homologous region located downstream of the wnt-1 gene in the pufferfish (Fugu rubripes). These sequences are capable of appropriate temporal and spatial activation of a reporter gene in the embryonic mouse midbrain; although, later aspects of the Wnt-1 expression pattern are absent. Genetic evidence has implicated Pax transcription factors in the regulation of Wnt-1. Although Pax-2 binds to the 110 base pair murine regulatory element in vitro, the location of the binding sites could not be precisely established and mutation of two putative low affinity sites did not abolish activation of a Wnt-1 reporter transgene in vivo. Thus, it is unlikely that Pax proteins regulate Wnt-1 by direct interactions with this cis-acting regulatory region. Our analysis of the 110 base pair minimal regulatory element suggests that Wnt-1 regulation is complex, involving different regulatory interactions for activation and the later maintenance of transgene expression in the dorsal midbrain and ventral diencephalon, and at the midbrain-hindbrain junction.

scholarly journals Molecular Genetic Analysis of Drosophila eyes absent Mutants Reveals an Eye Enhancer Element

Genetics ◽  
2000 ◽  
Vol 154 (1) ◽  
pp. 237-246
Author(s):  
John E Zimmerman ◽  
Quang T Bui ◽  
Haixi Liu ◽  
Nancy M Bonini
Keyword(s):  
Molecular Genetic ◽  
Regulatory Region ◽  
Ectopic Expression ◽  
Molecular Genetic Analysis ◽  
Regulatory Sequence ◽  
Enhancer Element ◽  
Eyes Absent ◽  
Extended Analysis ◽  
Cell Expression ◽  
Enhancer Sequences

Abstract The eyes absent (eya) gene is critical for normal eye development in Drosophila and is highly conserved to vertebrates. To define regions of the gene critical for eye function, we have defined the mutations in the four viable eya alleles. Two of these mutations are eye specific and undergo transvection with other mutations in the gene. These were found to be deletion mutations that remove regulatory sequence critical for eye cell expression of the gene. Two other viable alleles cause a reduced eye phenotype and affect the function of the gene in additional tissues, such as the ocelli. These mutations were found to be insertion mutations of different transposable elements within the 5′ UTR of the transcript. Detailed analysis of one of these revealed that the transposable element has become subject to regulation by eye enhancer sequences of the eya gene, disrupting normal expression of EYA in the eye. More extended analysis of the deletion region in the eye-specific alleles indicated that the deleted region defines an enhancer that activates gene expression in eye progenitor cells. This enhancer is responsive to ectopic expression of the eyeless gene. This analysis has defined a critical regulatory region required for proper eye expression of the eya gene.

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
Keyword(s):  
Specific Activity ◽  
Comparative Sequence Analysis ◽  
Limb Bud ◽  
Regulatory Sequence ◽  
Enhancer Element ◽  
Conserved Sequence ◽  
Intronic Enhancer ◽  
The Face ◽  
Multiple Structures

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.

scholarly journals Tissue-specific regulation of BMP signaling by Drosophila N-glycanase 1

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Antonio Galeone ◽  
Seung Yeop Han ◽  
Chengcheng Huang ◽  
Akira Hosomi ◽  
Tadashi Suzuki ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Bmp Signaling ◽  
Global Developmental Delay ◽  
Tissue Specific ◽  
Specific Loss ◽  
Functional Conservation ◽  
Visceral Mesoderm ◽  
Evolutionarily Conserved ◽  
Specific Regulation ◽  
High Degree

Mutations in the human N-glycanase 1 (NGLY1) cause a rare, multisystem congenital disorder with global developmental delay. However, the mechanisms by which NGLY1 and its homologs regulate embryonic development are not known. Here we show that Drosophila Pngl encodes an N-glycanase and exhibits a high degree of functional conservation with human NGLY1. Loss of Pngl results in developmental midgut defects reminiscent of midgut-specific loss of BMP signaling. Pngl mutant larvae also exhibit a severe midgut clearance defect, which cannot be fully explained by impaired BMP signaling. Genetic experiments indicate that Pngl is primarily required in the mesoderm during Drosophila development. Loss of Pngl results in a severe decrease in the level of Dpp homodimers and abolishes BMP autoregulation in the visceral mesoderm mediated by Dpp and Tkv homodimers. Thus, our studies uncover a novel mechanism for the tissue-specific regulation of an evolutionarily conserved signaling pathway by an N-glycanase enzyme.

scholarly journals Ctp1CtIP and Rad32Mre11 Nuclease Activity Are Required for Rec12Spo11 Removal, but Rec12Spo11 Removal Is Dispensable for Other MRN-Dependent Meiotic Functions

2009 ◽  
Vol 29 (7) ◽  
pp. 1671-1681 ◽  
Author(s):  
Edgar Hartsuiker ◽  
Kenichi Mizuno ◽  
Monika Molnar ◽  
Juerg Kohli ◽  
Kunihiro Ohta ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Chromatin Remodeling ◽  
Hot Spot ◽  
Nuclease Activity ◽  
Mrn Complex ◽  
Functional Conservation ◽  
Evolutionarily Conserved ◽  
Linear Elements ◽  
First Time

ABSTRACT The evolutionarily conserved Mre11/Rad50/Nbs1 (MRN) complex is involved in various aspects of meiosis. Whereas available evidence suggests that the Mre11 nuclease activity might be responsible for Spo11 removal in Saccharomyces cerevisiae, this has not been confirmed experimentally. This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32Mre11) nuclease activity is required for the removal of Rec12Spo11. Furthermore, we show that the CtIP homologue Ctp1 is required for Rec12Spo11 removal, confirming functional conservation between Ctp1CtIP and the more distantly related Sae2 protein from Saccharomyces cerevisiae. Finally, we show that the MRN complex is required for meiotic recombination, chromatin remodeling at the ade6-M26 recombination hot spot, and formation of linear elements (which are the equivalent of the synaptonemal complex found in other eukaryotes) but that all of these functions are proficient in a rad50S mutant, which is deficient for Rec12Spo11 removal. These observations suggest that the conserved role of the MRN complex in these meiotic functions is independent of Rec12Spo11 removal.

scholarly journals Emerging multifaceted roles of BAP1 complexes in biological processes

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Aileen Patricia Szczepanski ◽  
Lu Wang
Keyword(s):  
Transcriptional Repression ◽  
Target Genes ◽  
Regulatory Mechanisms ◽  
Biological Processes ◽  
Multiprotein Complex ◽  
Downstream Target ◽  
Evolutionarily Conserved ◽  
Complex Forms ◽  
Polycomb Repressive Complex 1

AbstractHistone H2AK119 mono-ubiquitination (H2AK119Ub) is a relatively abundant histone modification, mainly catalyzed by the Polycomb Repressive Complex 1 (PRC1) to regulate Polycomb-mediated transcriptional repression of downstream target genes. Consequently, H2AK119Ub can also be dynamically reversed by the BAP1 complex, an evolutionarily conserved multiprotein complex that functions as a general transcriptional activator. In previous studies, it has been reported that the BAP1 complex consists of important biological roles in development, metabolism, and cancer. However, identifying the BAP1 complex’s regulatory mechanisms remains to be elucidated due to its various complex forms and its ability to target non-histone substrates. In this review, we will summarize recent findings that have contributed to the diverse functional role of the BAP1 complex and further discuss the potential in targeting BAP1 for therapeutic use.

scholarly journals Roles of ncRNAs as ceRNAs in Gastric Cancer

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1036
Author(s):  
Junhong Ye ◽  
Jifu Li ◽  
Ping Zhao
Keyword(s):  
Gastric Cancer ◽  
Research Strategy ◽  
Circular Rnas ◽  
Messenger Rnas ◽  
Cerna Network ◽  
Degree Of Malignancy ◽  
High Degree ◽  
Competitive Endogenous Rna ◽  
Made In

Although ignored in the past, with the recent deepening of research, significant progress has been made in the field of non-coding RNAs (ncRNAs). Accumulating evidence has revealed that microRNA (miRNA) response elements regulate RNA. Long ncRNAs, circular RNAs, pseudogenes, miRNAs, and messenger RNAs (mRNAs) form a competitive endogenous RNA (ceRNA) network that plays an essential role in cancer and cardiovascular, neurodegenerative, and autoimmune diseases. Gastric cancer (GC) is one of the most common cancers, with a high degree of malignancy. Considerable progress has been made in understanding the molecular mechanism and treatment of GC, but GC’s mortality rate is still high. Studies have shown a complex ceRNA crosstalk mechanism in GC. lncRNAs, circRNAs, and pseudogenes can interact with miRNAs to affect mRNA transcription. The study of the involvement of ceRNA in GC could improve our understanding of GC and lead to the identification of potential effective therapeutic targets. The research strategy for ceRNA is mainly to screen the different miRNAs, lncRNAs, circRNAs, pseudogenes, and mRNAs in each sample through microarray or sequencing technology, predict the ceRNA regulatory network, and, finally, conduct functional research on ceRNA. In this review, we briefly discuss the proposal and development of the ceRNA hypothesis and the biological function and principle of ceRNAs in GC, and briefly introduce the role of ncRNAs in the GC’s ceRNA network.

Surgeon-performed Ultrasound for Primary Hyperparathyroidism

2013 ◽  
Vol 79 (7) ◽  
pp. 681-685 ◽  
Author(s):  
Worthington G. Schenk ◽  
John B. Hanks ◽  
Philip W. Smith
Keyword(s):  
Primary Hyperparathyroidism ◽  
Class 1 ◽  
Additional Imaging ◽  
Surgical Cure ◽  
Operative Findings ◽  
Enhanced Computed Tomography ◽  
High Degree ◽  
Tomography Scan ◽  
Parathyroid Imaging

The role of preoperative parathyroid imaging continues to evolve. This study evaluated whether surgeon-performed ultrasound (U/S) obviates the need for other imaging studies and leads to a focused exploration with a high degree of surgical success. From July 2010 to February 2012, 200 patients presenting with nonfamilial primary hyperparathyroidism underwent neck U/S in the surgeon's office. The U/S interpretation was classified as Class 1 if an adenoma was identified with high confidence, Class 2 if a possible but not definite enlarged gland was imaged, and Class 0 (zero) if no adenoma was identified. The findings were correlated with subsequent intra-operative findings. There were 144 Class 1 U/Ss (72%); of 132 patients coming to surgery, 96.2 per cent had surgical findings concordant with preoperative U/S and all had apparent surgical cure. Twenty-nine patients (14.5%) had Class 2 U/S; the 31 per cent confirmed false-positives in this group were usually colloid nodules. Fourteen of 27 with Class 0 U/S underwent surgery after being offered dynamically enhanced computed tomography scan. All 200 patients were apparent surgical cures. Surgeon-performed U/S is expedient, convenient, inexpensive, and accurate. A clearly identified adenoma can safely lead to a focused limited exploration and avoid additional imaging 93 per cent of the time.

The academic profession in Russia’s two capitals: The impact of 20 years of transition

2017 ◽  
Vol 16 (5) ◽  
pp. 626-644 ◽  
Author(s):  
Elizaveta Sivak ◽  
Maria Yudkevich
Keyword(s):  
Large Scale ◽  
Academic Career ◽  
Academic Profession ◽  
University Faculty ◽  
Key Characteristics ◽  
Personal Strain ◽  
High Degree ◽  
The Impact ◽  
Russian Universities

This paper studies the dynamics of key characteristics of the academic profession in Russia based on the analysis of university faculty in the two largest cities in Russia – Moscow and St Petersburg. We use data on Russian university faculty from two large-scale comparative studies of the academic profession (‘The Carnegie Study’ carried out in 1992 in 14 countries, including Russia, and ‘The Changing Academic Profession Study’, 2007–2012, with 19 participating countries and which Russia joined in 2012) to look at how faculty’s characteristics and attitudes toward different aspects of their academic life changed over 20 years (1992–2011) such as faculty’s views on reasons to leave or to stay at a university, on university’s management and the role of faculty in decision making. Using the example of universities in the two largest Russian cities, we demonstrate that the high degree of overall centralization of governance in Russian universities barely changed in 20 years. Our paper provides comparisons of teaching/research preferences and views on statements concerning personal strain associated with work, academic career perspectives, etc., not only in Russian universities between the years 1992 and 2012, but also in Russia and other ‘Changing Academic Profession’ countries.

Myocardial CO2 buffering: role of transmembrane transport of H+ or HCO3-ions

1976 ◽  
Vol 230 (4) ◽  
pp. 1037-1041 ◽  
Author(s):  
DR Strome ◽  
RL Clancy ◽  
NC Gonzalez
Keyword(s):  
Small Volume ◽  
Coronary Circulation ◽  
Myocardial Cell ◽  
Ringer Solution ◽  
Red Cells ◽  
Transmembrane Transport ◽  
High Degree

Isolated rabbit hearts were perfused with rabbit red cells suspended in Ringer solution. A small volume of perfusate was recirculated for 10 min at Pco2 of 33.4 +/- 0.9 or 150.8 +/- 7.5 mmHg. Hypercapnia resulted in an increase in perfusate HCO3- concentration that was smaller than that observed when isolated perfusate was equilibrated in vitro with the same CO2 tensions (delta HCO-3e = 1.6 mM, P less than 0.01). This difference is consistent with a net movement of HCO3- into or H+ out of the mycardial cell, and cannot be accounted for by dilution of HCO3- in the myocardial interstitium. Recirculation of perfusate through the coronary circulation at normal Pco2 for two consecutive 10-min periods was not followed by changes in perfusate HCO3- concentration. A high degree of correlation (r = 0.81) was observed between intracellular HCO-3e concentration and the corresponding delta HCO-3e in individual experiments. The results suggest that transmembrane exchange of H+ or HCO3- is a buffer mechanism for CO2 in the myocardial cell.

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