scholarly journals Functional significance of Sp1, Sp2, and Sp3 transcription factors in regulation of the murine CTP:phosphocholine cytidylyltransferase α promoter

2000 ◽  
Vol 41 (4) ◽  
pp. 583-594 ◽  
Author(s):  
Marica Bakovic ◽  
Kristin A. Waite ◽  
Dennis E. Vance
Keyword(s):  
Transcription Factors ◽  
Functional Significance ◽  
Ctp:Phosphocholine Cytidylyltransferase

scholarly journals Co-option of the Limb Patterning Program in Cephalopod Lens Development

2021 ◽  
Author(s):  
Stephanie Neal ◽  
Kyle J. McCulloch ◽  
Francesca Napoli ◽  
Christina M. Daly ◽  
James H. Coleman ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Wnt Signaling ◽  
Functional Significance ◽  
Limb Development ◽  
Lens Development ◽  
Limb Patterning ◽  
Regulatory Relationship ◽  
Radial Patterning ◽  
Underlying Mechanisms

AbstractAcross the Metazoa, similar genetic programs are found in the development of analogous, independently evolved, morphological features. The functional significance of this reuse and the underlying mechanisms of co-option remain unclear. Here we identify the co-option of the canonical bilaterian limb pattering program redeployed during cephalopod lens development, a functionally unrelated structure. We show radial expression of transcription factorsSP6-9/sp1, Dlx/dll, Pbx/exd, Meis/hth, and aPrdlhomolog in the squidDoryteuthis pealeii, similar to expression required inDrosophilalimb development. We assess the role of Wnt signaling in the cephalopod lens, a positive regulator in the developing limb, and find the regulatory relationship reversed, with ectopic Wnt signaling leading to lens loss. This regulatory divergence suggests that duplication of SP6-9 in cephalopods may mediate this co-option. These results suggest that the limb network does not exclusively pattern appendage outgrowth but is performing a more universal developmental function: radial patterning.

scholarly journals Exploratory Investigation on Functional Significance ofETS2andSIM2Genes in Down Syndrome

2011 ◽  
Vol 31 (5) ◽  
pp. 247-257 ◽  
Author(s):  
Arpita Chatterjee ◽  
Samikshan Dutta ◽  
Swagata Sinha ◽  
Kanchan Mukhopadhyay
Keyword(s):  
Down Syndrome ◽  
Transcription Factors ◽  
Functional Significance ◽  
Genomic Dna ◽  
Nonsynonymous Substitution ◽  
Regulatory Genes ◽  
Statistical Analyses ◽  
Exploratory Investigation

Trisomy of the 21st chromosome leads to an over dosage of several regulatory genes in Down syndrome (DS). Though allelic and genotypic combinations formed between genes are interesting, till date, this particular area has never been explored in DS. In the present investigation four SNPs in two transcription factors, Single minded 2 (SIM2) and V-ets erythroblastosis virus E26 oncogene homolog2 (ETS2), located in the 21st chromosome were genotyped to understand their role in DS. Genomic DNA of eastern Indian probands with DS (N= 132), their parents (N= 209) and ethnically matched controls (N= 149) was subjected to PCR-based analyses of functionally important SNPs followed by statistical analyses.ETS2rs461155 showed high heterozygosity in DS. Significantly lower frequency ofSIM2C-G haplotype (rs2073601-rs2073416) was noticed in individuals with DS (Pvalue = 0.01669) and their fathers (Pvalue = 0.01185). Significantly lower frequency of the A-C-C-G with higher frequency of A-C-A-G haplotypes was also noticed in subjects with DS (Pvalue = 0.02089 and 0.00588 respectively). Data obtained indicate that the rs2073601 ‘A’ allele, responsible for nonsynonymous substitution of leucine to methionine, may have some role in DS in this population.

Abstract 264: Upstream and Downstream Regulators of Lysophosphatidic Acid Receptor 4 are Critical for Cardiac Differentiation and Repair

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Hyun-jai Cho ◽  
Jin-Woo Lee ◽  
Choon-Soo Lee ◽  
Hyo-Soo Kim
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Lysophosphatidic Acid ◽  
Functional Significance ◽  
Cardiac Differentiation ◽  
Specific Marker ◽  
Acid Receptor ◽  
Lysophosphatidic Acid Receptor ◽  
Human Ipscs

The therapeutic application of cell therapy to repair the damaged heart requires a comprehensive understanding of the process of cardiac differentiation of stem cells. We discovered a cardiac-specific marker, lysophosphatidic acid receptor 4 (LPAR4), which is G protein-coupled receptor (GPCR) and demonstrated its functional significance during cardiac differentiation. We screened GPCR expressing on mouse cardiac progenitor cells at differentiation day 3 compared to mouse undifferentiated pluripotent stem cells (PSCs). Among candidates, we identified LPAR4. We have found that in both mouse and human PSCs, LPAR4 has a transient expression pattern during cardiac differentiation. During in vitro differentiation of mouse and human PSCs toward cardiomyocytes, LPAR4 expression peaked for 3-5 days and then and declined immediately. Treatment with ODP (LPAR4 specific agonist) followed by p38MAPK blocker (SB203580) in the cardiac differentiation protocol significantly increased cardiac differentiation efficiency. Then we performed RNA sequencing to find transcription factors that regulate LPAR4. We screened 2-fold up-regulated transcription factors that related to cardiac differentiation during human iPSCs toward cardiomyocytes. The expression of LPAR4 is regulated by SOX17 expression, demonstrating that SOX17 is an upstream regulator of LPAR4. During cardiac differentiation, when knocking down SOX17 by siRNA, the expression of LPAR4 decreased as the expression of SOX17 mRNA decreased, resulting in no progression of cardiac differentiation. Besides, cardiac differentiation did not progress when SOX17 was overexpressed. SOX17 plays a role early in cardiac differentiation and that the expression should be reduced. However, it is assumed that sox17 lentivirus was gene-integrated and continued expression without decreasing expression. SOX17 overexpression needs further study. In conclusion, we demonstrated that LPAR4 is a novel cardiac progenitor cell marker and modulation of the upstream and downstream regulators shown functional significance during cardiac differentiation. Furthermore, our findings provide new insight into cell-free cardiac repair by the modulation of LPAR4 positive cells in the heart. Funding Source: This study was supported by "Strategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer" (HI17C2085) through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea.

scholarly journals Modulation of DNA topoisomerase IIα promoter activity by members of the Sp (specificity protein) and NF-Y (nuclear factor Y) families of transcription factors

2003 ◽  
Vol 374 (3) ◽  
pp. 723-729 ◽  
Author(s):  
Natisha MAGAN ◽  
Agnieszka P. SZREMSKA ◽  
Richard J. ISAACS ◽  
Kathryn M. STOWELL
Keyword(s):  
Transcription Factors ◽  
Functional Significance ◽  
Regulatory Elements ◽  
Resistant Cell ◽  
Nuclear Factor ◽  
Drug Resistant ◽  
Topoisomerase Iiα ◽  
Nuclear Factor Y ◽  
Specificity Protein ◽  
Drug Resistant Cell

topo IIα (topoisomerase IIα) is a major target of several commonly used anticancer drugs and is subject to down-regulation at the transcriptional level in some drug-resistant cell lines and tumours in response to chemotherapy. Clinical resistance to such drugs has been correlated with down-regulation of topo IIα at transcription in some drug-resistant cell lines and tumours. Putative binding sites for a variety of transcription factors, including Sp1 (specificity protein 1) and NF-Y (nuclear factor Y) have previously been identified in the topo IIα promoter, but their functional significance and interactions have not been described following exposure to anti-cancer drugs. The binding of these factors to specific putative regulatory elements in the topo IIα promoter was studied using electrophoretic-mobility-shift assays. Sp1 was found to bind strongly to both distal and proximal GC-rich elements and NF-Y to ICB1 (the first inverted CCAAT box). The functional significance of transcription-factor binding was studied using transient transfection of HeLa cells using a luciferase reporter driven by a 617-bp minimal promoter containing point mutations in putative regulatory elements. Sp1 and NF-Y were both found to be transcriptional modulators with activator or repressor functions depending on protein/DNA context. Moreover, a functional interaction between Sp1 and NF-Y bound at proximal elements was observed.

scholarly journals The Functional Significance of Common Polymorphisms in Zinc Finger Transcription Factors

2014 ◽  
Vol 4 (9) ◽  
pp. 1647-1655 ◽  
Author(s):  
S. H. Lockwood ◽  
A. Guan ◽  
A. S. Yu ◽  
C. Zhang ◽  
A. Zykovich ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Zinc Finger ◽  
Functional Significance

Functional significance of preserved color patterns of mollusks from the Gosport Sand (Eocene) of Alabama

1988 ◽  
Vol 62 (01) ◽  
pp. 83-87 ◽  
Author(s):  
Patricia H. Kelley ◽  
Charles T. Swann
Keyword(s):  
Functional Morphology ◽  
Functional Significance ◽  
Intraspecific Variability ◽  
Color Pattern ◽  
Color Patterns ◽  
Historical Factors ◽  
Life Mode ◽  
Molluscan Fauna ◽  
Excellent Preservation ◽  
Architectural Constraints

The excellent preservation of the molluscan fauna from the Gosport Sand (Eocene) at Little Stave Creek, Alabama, has made it possible to describe the preserved color patterns of 15 species. In this study the functional significance of these color patterns is tested in the context of the current adaptationist controversy. The pigment of the color pattern is thought to be a result of metabolic waste disposal. Therefore, the presence of the pigment is functional, although the patterns formed by the pigment may or may not have been adaptive. In this investigation the criteria proposed by Seilacher (1972) for testing the functionality of color patterns were applied to the Gosport fauna and the results compared with life mode as interpreted from knowledge of extant relatives and functional morphology. Using Seilacher's criteria of little ontogenetic and intraspecific variability, the color patterns appear to have been functional. However, the functional morphology studies indicate an infaunal life mode which would preclude functional color patterns. Particular color patterns are instead interpreted to be the result of historical factors, such as multiple adaptive peaks or random fixation of alleles, or of architectural constraints including possibly pleiotropy or allometry. The low variability of color patterns, which was noted within species and genera, suggests that color patterns may also serve a useful taxonomic purpose.

Complex Vesicles, Microtubules, and Cytoplasmic Filaments in the Endothelial Cells of Normal Dog Aorta

1968 ◽  
Vol 26 ◽  
pp. 172-173
Author(s):  
C. N. Sun ◽  
J. J. Ghidoni
Keyword(s):  
Electron Microscopy ◽  
Endothelial Cells ◽  
Cross Sections ◽  
Functional Significance ◽  
Tubular Structures ◽  
Aldehyde Fixation ◽  
Cytoplasmic Filaments

Endothelial cells in longitudinal and cross sections of aortas from 3 randomly selected “normal” mongrel dogs were studied by electron microscopy. Segments of aorta were distended with cold cacodylate buffered 5% glutaraldehyde for 10 minutes prior to being cut into small, well oriented tissue blocks. After an additional 1-1/2 hour period in glutaraldehyde, the tissue blocks were well rinsed in buffer and post-fixed in OsO4. After dehydration they were embedded in a mixture of Maraglas, D.E.R. 732, and DDSA.Aldehyde fixation preserves the filamentous and tubular structures (300 Å and less) for adequate demonstration and study. The functional significance of filaments and microtubules has been recently discussed by Buckley and Porter; the precise roles of these cytoplasmic components remains problematic. Endothelial cells in canine aortas contained an abundance of both types of structures.

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