scholarly journals Using a phiC31 “Disintegrase” to make new attP sites in the Drosophila genome at locations showing chromosomal position effects

PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0205538 ◽  
Author(s):  
Mukesh Maharjan ◽  
Robert K. Maeda ◽  
François Karch ◽  
Craig M. Hart
Keyword(s):  
Drosophila Genome ◽  
Position Effects ◽  
Chromosomal Position

scholarly journals Deletion of an Insulator Element by the Mutation facet-strawberry in Drosophila melanogaster

Genetics ◽  
2000 ◽  
Vol 155 (3) ◽  
pp. 1297-1311
Author(s):  
Julio Vazquez ◽  
Paul Schedl
Keyword(s):  
Drosophila Melanogaster ◽  
Boundary Element ◽  
Structural Organization ◽  
Position Effects ◽  
Genetic Studies ◽  
Small Deletion ◽  
Chromosomal Position ◽  
Insulator Element ◽  
Functional Autonomy ◽  
Dna Fragment

Abstract Eukaryotic chromosomes are thought to be subdivided into a series of structurally and functionally independent units. Critical to this hypothesis is the identification of insulator or boundary elements that delimit chromosomal domains. The properties of a Notch mutation, facet-strawberry (faswb), suggest that this small deletion disrupts such a boundary element. faswb is located in the interband separating polytene band 3C7, which contains Notch, from the distal band 3C6. The faswb mutation alters the structural organization of the chromosome by deleting the interband and fusing 3C7 with 3C6. Genetic studies also suggest that faswb compromises the functional autonomy of Notch by allowing the locus to become sensitive to chromosomal position effects emanating from distal sequences. In the studies reported here, we show that a DNA fragment spanning the faswb region can insulate reporter transgenes against chromosomal position effects and can block enhancer-promoter interactions. Moreover, we find that insulating activity is dependent on sequences deleted in faswb. These results provide evidence that the element defined by the faswb mutation corresponds to an insulator.

scholarly journals A chromatin insulator protects retrovirus vectors from chromosomal position effects

2000 ◽  
Vol 97 (16) ◽  
pp. 9150-9155 ◽  
Author(s):  
D. W. Emery ◽  
E. Yannaki ◽  
J. Tubb ◽  
G. Stamatoyannopoulos
Keyword(s):  
Position Effects ◽  
Chromatin Insulator ◽  
Chromosomal Position

Poly(dC?dA/dG?dT) repeats in the Drosophila genome: a key function for dosage compensation and position effects?

Chromosoma ◽  
1987 ◽  
Vol 95 (3) ◽  
pp. 209-215 ◽  
Author(s):  
Peter Huijser ◽  
Wolfgang Hennig ◽  
Rosilde Dijkhof
Keyword(s):  
Dosage Compensation ◽  
Drosophila Genome ◽  
Position Effects

The degree of phenotypic correction of murine β-thalassemia intermedia following lentiviral-mediated transfer of a human γ-globin gene is influenced by chromosomal position effects and vector copy number

Blood ◽  
2003 ◽  
Vol 101 (6) ◽  
pp. 2175-2183 ◽  
Author(s):  
Derek A. Persons ◽  
Phillip W. Hargrove ◽  
Esther R. Allay ◽  
Hideki Hanawa ◽  
Arthur W. Nienhuis
Keyword(s):  
Copy Number ◽  
Lentiviral Vector ◽  
Globin Gene ◽  
Erythroid Cell ◽  
Thalassemia Intermedia ◽  
Globin Mrna ◽  
Position Effects ◽  
Chromosomal Position ◽  
Vector Copy Number ◽  
Globin Promoter

Increased fetal hemoglobin (HbF) levels diminish the clinical severity of β-thalassemia and sickle cell anemia. A treatment strategy using autologous stem cell–targeted gene transfer of a γ-globin gene may therefore have therapeutic potential. We evaluated oncoretroviral- and lentiviral-based γ-globin vectors for expression in transduced erythroid cell lines. Compared with γ-globin, oncoretroviral vectors containing either a β-spectrin or β-globin promoter and the α-globin HS40 element, a γ-globin lentiviral vector utilizing the β-globin promoter and elements from the β-globin locus control region demonstrated a higher probability of expression. This lentiviral vector design was evaluated in lethally irradiated mice that received transplants of transduced bone marrow cells. Long-term, stable erythroid expression of human γ-globin was observed with levels of vector-encoded γ-globin mRNA ranging from 9% to 19% of total murine α-globin mRNA. The therapeutic efficacy of the vector was subsequently evaluated in a murine model of β-thalassemia intermedia. The majority of mice that underwent transplantation expressed significant levels of chimeric mα2hγ2molecules (termed HbF), the amount of which correlated with the degree of phenotypic improvement. A group of animals with a mean HbF level of 21% displayed a 2.5 g/dL (25 g/L) improvement in Hb concentration and normalization of erythrocyte morphology relative to control animals. γ-Globin expression and phenotypic improvement was variably lower in other animals due to differences in vector copy number and chromosomal position effects. These data establish the potential of using a γ-globin lentiviral vector for gene therapy of β-thalassemia.

scholarly journals Chromosomal Position Effects Reveal Different cis-Acting Requirements for rDNA Transcription and Sex Chromosome Pairing in Drosophila melanogaster

Genetics ◽  
2000 ◽  
Vol 155 (3) ◽  
pp. 1195-1211 ◽  
Author(s):  
Albert Briscoe ◽  
John E Tomkiel
Keyword(s):  
Drosophila Melanogaster ◽  
Chromosome Pairing ◽  
Sex Chromosome ◽  
Position Effect ◽  
Meiotic Pairing ◽  
Rdna Transcription ◽  
Position Effects ◽  
Cis Acting ◽  
Chromosomal Position ◽  
Rdna Loci

Abstract In Drosophila melanogaster, the rDNA loci function in ribosome biogenesis and nucleolar formation and also as sex chromosome pairing sites in male meiosis. These activities are not dependent on the heterochromatic location of the rDNA, because euchromatic transgenes are competent to form nucleoli and restore pairing to rDNA-deficient X chromosomes. These transgene studies, however, do not address requirements for the function of the endogenous rDNA loci within the heterochromatin. Here we describe two chromosome rearrangements that disrupt rDNA functions. Both rearrangements are translocations that cause an extreme bobbed visible phenotype and XY nondisjunction and meiotic drive in males. However, neither rearrangement interacts with a specific Y chromosome, Ymal+, that induces male sterility in combination with rDNA deletions. Molecular studies show that the translocations are not associated with gross rearrangements of the rDNA repeat arrays. Rather, suppression of the bobbed phenotypes by Y heterochromatin suggests that decreased rDNA function is caused by a chromosomal position effect. While both translocations affect rDNA transcription, only one disrupts meiotic XY pairing, indicating that there are different cis-acting requirements for rDNA transcription and rDNA-mediated meiotic pairing.

Polycomb Group Repression Is Blocked by the Drosophila suppressor of Hairy-wing [su(Hw)] Insulator

Genetics ◽  
1998 ◽  
Vol 148 (1) ◽  
pp. 331-339
Author(s):  
Daniel R Mallin ◽  
Jane S Myung ◽  
J Scott Patton ◽  
Pamela K Geyer
Keyword(s):  
Reporter Genes ◽  
Polycomb Group ◽  
Polycomb Group Proteins ◽  
Binding Region ◽  
Position Effects ◽  
Response Element ◽  
Polycomb Group Genes ◽  
Chromosomal Position ◽  
Group Response

Abstract The suppressor of Hairy-wing [SU(HW)] binding region disrupts communication between a large number of enhancers and promoters and protects transgenes from chromosomal position effects. These properties classify the SU(HW) binding region as an insulator. While enhancers are blocked in a general manner, protection from repressors appears to be more variable. In these studies, we address whether repression resulting from the Polycomb group genes can be blocked by the SU(HW) binding region. The effects of this binding region on repression established by an Ultrabithorax Polycomb group Response Element were examined. A transposon carrying two reporter genes, the yellow and white genes, was used so that repression and insulation could be assayed simultaneously. We demonstrate that the SU(HW) binding region is effective at preventing Polycomb group repression. These studies suggest that one role of the su(Hw) protein may be to restrict the range of action of repressors, such as the Polycomb group proteins, throughout the euchromatic regions of the genome.

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