scholarly journals High Level of Structural Polymorphism Driven by Mobile Elements in the Hox Genomic Region of the Chaetognath Spadella cephaloptera

2010 ◽  
Vol 2 ◽  
pp. 665-667 ◽  
Author(s):  
Ferdinand Marlétaz ◽  
Gabor Gyapay ◽  
Yannick Le Parco
Keyword(s):  
Genomic Region ◽  
Mobile Elements ◽  
Structural Polymorphism ◽  
Spadella Cephaloptera ◽  
High Level

Autoregulation of MEIS1 through a Distal Enhancer in Acute Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 745-745
Author(s):  
Qianfei Wang ◽  
Jingfang Dong ◽  
Ryan Mattison ◽  
Shyam Prabhakar ◽  
Fabio Eiji Arimura ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cell Lines ◽  
Reporter Gene ◽  
Genomic Region ◽  
Regulatory Function ◽  
Distal Enhancer ◽  
Enhancer Element ◽  
Two Factors ◽  
High Level

Abstract Aberrant activation of the TALE (three-amino-acid loop extension) homeobox gene MEIS1 is frequently observed in acute leukemia. A high level of Meis1 expression shortens the latency, as well as accelerates the onset and progression of acute myeloid leukemia in mice. Although available data support the notion that MEIS1 is oncogenic by means of overexpression rather than mutation, the molecular mechanism underlying persistent activation of this gene in leukemia remains poorly understood. We have identified a distal enhancer (designated EX) at the MEIS1 locus and found that MEIS1 itself and HOXA9 synergistically activate the regulatory activity of EX through a conserved DNA motif. Using comparative genomics-based strategies, we computationally predicted 14 putative enhancer DNA elements in the 1300 Kb MEIS1 locus. We confirmed that the human sequences of 6 of these 14 elements showed enhancer function as they were able to direct GFP expression in a spatiotemporal manner during embryonic hematopoiesis in an in vivo transgenic zebrafish assay. To explore whether these 6 elements play a role in regulating MEIS1 expression in human leukemia, we examined the presence of histone modifications that are associated with gene activation in a panel of 8 leukemia cell lines. In MEIS1-expressing cells, but not MEIS1 transcript-negative cell lines, the genomic region corresponding to enhancer EX showed extensive H3K4 mono-methylation (me1H3K4), a hallmark of active distal enhancers. When endogenous MEIS1 expression decreases during cellular differentiation, the active histone mark me1H3K4 was replaced by repressive H3K27 methylation and the associated EZH2 polycomb protein at the EX region. In murine leukemia models, retroviral integration at the Meis1 locus has been shown to result in overexpression of Meis1 leading to development of AML. Strikingly, we found that viral integration frequently occurred within the genomic sequence corresponding to enhancer EX. Collectively, these data suggest that enhancer EX plays an important role in maintaining high level expression of endogenous MEIS1 in transformed leukemic cells. In an effort to identify the molecular basis underlying the observed regulatory function of EX, we found MEIS1 and HOXA9 synergistically stimulate the enhancer activity of EX in reporter gene assays, suggesting that production of MEIS1 protein can reinforce its own expression. Mutation of a conserved site within the enhancer abolished the ability of these two factors to activate reporter gene expression. Using ChIP (Chromatin Immunoprecipitation), we further demonstrated that MEIS1 and HOXA9 specifically bind to the genomic region containing the conserved site in vivo, and the presence of these two factors in the region is associated with active MEIS1 expression. These studies provide insight on the molecular mechanisms controlling transcription regulation of MEIS1, suggesting that overexpression of MEIS1 in acute leukemia is sustained by an autoregulatory loop mediated through a distal enhancer element.

scholarly journals Evidence for Redundancy But Not trans Factor-cis Element Coevolution in the Regulation of Drosophila Yp Genes

Genetics ◽  
1999 ◽  
Vol 152 (2) ◽  
pp. 605-616
Author(s):  
Fabio Piano ◽  
Michael J Parisi ◽  
Roger Karess ◽  
Michael P Kambysellis
Keyword(s):  
Intergenic Region ◽  
Fat Body ◽  
Ectopic Expression ◽  
Genomic Region ◽  
Specific Pattern ◽  
Sequence Comparisons ◽  
Cis Acting ◽  
Accurate Expression ◽  
High Level

Abstract In Drosophila melanogaster and the endemic Hawaiian species D. grimshawi three Yolk protein (Yp) genes are expressed in a similar sex- and tissue-specific pattern. In contrast, DNA sequence comparisons of promoter/enhancer regions show low levels of similarity. We tested the functional significance of these observations by transforming D. melanogaster with the genomic region that includes the divergently transcribed D. grimshawi DgYp1 and DgYp2 genes; we found that the introduced genes were expressed in female fat body and in ovaries but not in males. Moreover, we found D. grimshawi proteins in the hemolymph and accumulating in ovaries. Using reporter constructs we showed that the intergenic region from D. grimshawi was sufficient to drive accurate expression, but some low level of ectopic expression was seen in males. Transforming D. melanogaster with constructs bearing deletions within the D. grimshawi intergenic region revealed only subtle effects in the overall level of expression, suggesting a high level of redundancy. Testing mutants in the sex-specific regulator doublesex revealed that it is capable of repressing the DgYp genes in males. Together, these data show that D. melanogaster trans-acting factors can regulate the in vivo pattern of DgYp expression and support the notion of a redundant and complex system of cis-acting elements.

scholarly journals Physiological impact of transposable elements encoding DDE transposases in the environmental adaptation of Streptococcus agalactiae

Microbiology ◽  
2014 ◽  
Vol 160 (7) ◽  
pp. 1298-1315 ◽  
Author(s):  
Maud Fléchard ◽  
Philippe Gilot
Keyword(s):  
Transposable Elements ◽  
Streptococcus Agalactiae ◽  
Virulence Genes ◽  
Integration Site ◽  
Genomic Region ◽  
Mobile Elements ◽  
Conjugative Transposons ◽  
New Gene ◽  
Physiological Impact

We have referenced and described Streptococcus agalactiae transposable elements encoding DDE transposases. These elements belonged to nine families of insertion sequences (ISs) and to a family of conjugative transposons (TnGBSs). An overview of the physiological impact of the insertion of all these elements is provided. DDE-transposable elements affect S. agalactiae in a number of aspects of its capability to adapt to various environments and modulate the expression of several virulence genes, the scpB–lmB genomic region and the genes involved in capsule expression and haemolysin transport being the targets of several different mobile elements. The referenced mobile elements modify S. agalactiae behaviour by transferring new gene(s) to its genome, by modifying the expression of neighbouring genes at the integration site or by promoting genomic rearrangements. Transposition of some of these elements occurs in vivo, suggesting that by dynamically regulating some adaptation and/or virulence genes, they improve the ability of S. agalactiae to reach different niches within its host and ensure the ‘success’ of the infectious process.

Human polymorphism of P-selectin glycoprotein ligand 1 attributable to variable numbers of tandem decameric repeats in the mucinlike region

Blood ◽  
2001 ◽  
Vol 97 (10) ◽  
pp. 3306-3307 ◽  
Author(s):  
Vahid Afshar-Kharghan ◽  
Reyhan Diz-Küçükkaya ◽  
Erwin H. Ludwig ◽  
Ali J. Marian ◽  
José A. López
Keyword(s):  
Human Population ◽  
Polymerase Chain Reaction Amplification ◽  
Variable Number ◽  
Genomic Region ◽  
Structural Polymorphism ◽  
Functional Variation ◽  
Reaction Amplification ◽  
Human Polymorphism ◽  
Polymerase Chain ◽  
Tandem Repeat Polymorphism

Abstract Platelet GP Ibα and leukocyte P-selectin glycoprotein ligand 1 (PSGL-1) are membrane mucins with a number of structural and functional similarities. It was investigated whether, like GP Ibα, PSGL-1 is affected by a variable number of tandem repeat polymorphism in its mucin-like region. By polymerase chain reaction amplification of the genomic region encoding the PSGL-1 repeats, 3 allelic variants were identified in the human population. The 3 alleles—A, B, and C—from largest to smallest, contained 16, 15, and 14 decameric repeats, respectively, with the B variant lacking repeat 2 and the C variant retaining repeat 2 but lacking repeats 9 and 10. Allele frequencies were highest for the A variant and lowest for the C variant in the 2 populations studied (frequencies of 0.81, 0.17, and 0.02 in white persons and 0.65, 0.35, and 0.00 in Japanese). Thus, PSGL-1 is highly polymorphic and contains a structural polymorphism that potentially indicates functional variation in the human population.

Transcription factor/DNA interactions visualized by electron spectroscopic imaging

1992 ◽  
Vol 50 (1) ◽  
pp. 450-451
Author(s):  
David P. Bazett-Jones ◽  
Mark L. Brown
Keyword(s):  
Transcription Factor ◽  
Dna Sequences ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Phosphorus Content ◽  
Spectroscopic Imaging ◽  
Electron Spectroscopic Imaging ◽  
Dna Backbone ◽  
Two Parameters ◽  
High Level

A multisubunit RNA polymerase enzyme is ultimately responsible for transcription initiation and elongation of RNA, but recognition of the proper start site by the enzyme is regulated by general, temporal and gene-specific trans-factors interacting at promoter and enhancer DNA sequences. To understand the molecular mechanisms which precisely regulate the transcription initiation event, it is crucial to elucidate the structure of the transcription factor/DNA complexes involved. Electron spectroscopic imaging (ESI) provides the opportunity to visualize individual DNA molecules. Enhancement of DNA contrast with ESI is accomplished by imaging with electrons that have interacted with inner shell electrons of phosphorus in the DNA backbone. Phosphorus detection at this intermediately high level of resolution (≈lnm) permits selective imaging of the DNA, to determine whether the protein factors compact, bend or wrap the DNA. Simultaneously, mass analysis and phosphorus content can be measured quantitatively, using adjacent DNA or tobacco mosaic virus (TMV) as mass and phosphorus standards. These two parameters provide stoichiometric information relating the ratios of protein:DNA content.

Advances in Stem Instrumentation for Biology

1990 ◽  
Vol 48 (1) ◽  
pp. 362-363
Author(s):  
J. S. Wall
Keyword(s):  
Scanning Transmission Electron Microscope ◽  
Carbon Films ◽  
Specimen Preparation ◽  
Material Deposition ◽  
Active User ◽  
Percent Improvement ◽  
Scanning Transmission ◽  
The Moment ◽  
Film Substrate ◽  
High Level

The forte of the Scanning transmission Electron Microscope (STEM) is high resolution imaging with high contrast on thin specimens, as demonstrated by visualization of single heavy atoms. of equal importance for biology is the efficient utilization of all available signals, permitting low dose imaging of unstained single molecules such as DNA.Our work at Brookhaven has concentrated on: 1) design and construction of instruments optimized for a narrow range of biological applications and 2) use of such instruments in a very active user/collaborator program. Therefore our program is highly interactive with a strong emphasis on producing results which are interpretable with a high level of confidence.The major challenge we face at the moment is specimen preparation. The resolution of the STEM is better than 2.5 A, but measurements of resolution vs. dose level off at a resolution of 20 A at a dose of 10 el/A2 on a well-behaved biological specimen such as TMV (tobacco mosaic virus). To track down this problem we are examining all aspects of specimen preparation: purification of biological material, deposition on the thin film substrate, washing, fast freezing and freeze drying. As we attempt to improve our equipment/technique, we use image analysis of TMV internal controls included in all STEM samples as a monitor sensitive enough to detect even a few percent improvement. For delicate specimens, carbon films can be very harsh-leading to disruption of the sample. Therefore we are developing conducting polymer films as alternative substrates, as described elsewhere in these Proceedings. For specimen preparation studies, we have identified (from our user/collaborator program ) a variety of “canary” specimens, each uniquely sensitive to one particular aspect of sample preparation, so we can attempt to separate the variables involved.

A Questionnaire Survey of Current Rehabilitation Practices for Adults With Normal Hearing Sensitivity Who Experience Auditory Difficulties

2020 ◽  
Vol 29 (4) ◽  
pp. 738-761
Author(s):  
Tess K. Koerner ◽  
Melissa A. Papesh ◽  
Frederick J. Gallun
Keyword(s):  
Hearing Aids ◽  
Questionnaire Survey ◽  
Patient Population ◽  
Clinical Care ◽  
Normal Hearing ◽  
Auditory Training ◽  
Training Methods ◽  
Hearing Sensitivity ◽  
Considerable Benefit ◽  
High Level

Purpose A questionnaire survey was conducted to collect information from clinical audiologists about rehabilitation options for adult patients who report significant auditory difficulties despite having normal or near-normal hearing sensitivity. This work aimed to provide more information about what audiologists are currently doing in the clinic to manage auditory difficulties in this patient population and their views on the efficacy of recommended rehabilitation methods. Method A questionnaire survey containing multiple-choice and open-ended questions was developed and disseminated online. Invitations to participate were delivered via e-mail listservs and through business cards provided at annual audiology conferences. All responses were anonymous at the time of data collection. Results Responses were collected from 209 participants. The majority of participants reported seeing at least one normal-hearing patient per month who reported significant communication difficulties. However, few respondents indicated that their location had specific protocols for the treatment of these patients. Counseling was reported as the most frequent rehabilitation method, but results revealed that audiologists across various work settings are also successfully starting to fit patients with mild-gain hearing aids. Responses indicated that patient compliance with computer-based auditory training methods was regarded as low, with patients generally preferring device-based rehabilitation options. Conclusions Results from this questionnaire survey strongly suggest that audiologists frequently see normal-hearing patients who report auditory difficulties, but that few clinicians are equipped with established protocols for diagnosis and management. While many feel that mild-gain hearing aids provide considerable benefit for these patients, very little research has been conducted to date to support the use of hearing aids or other rehabilitation options for this unique patient population. This study reveals the critical need for additional research to establish evidence-based practice guidelines that will empower clinicians to provide a high level of clinical care and effective rehabilitation strategies to these patients.

805: High-Level Cyclin D1 is Associated with High Gleason Grade and Predicts Worse Biochemical-Free Survival in Prostate Cancer

2006 ◽  
Vol 175 (4S) ◽  
pp. 260-260
Author(s):  
Rile Li ◽  
Hong Dai ◽  
Thomas M. Wheeler ◽  
Anna Frolov ◽  
Gustavo Ayala
Keyword(s):  
Prostate Cancer ◽  
Cyclin D1 ◽  
Gleason Grade ◽  
Free Survival ◽  
High Level
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