scholarly journals Heterozygous Triplication of Upstream Regulatory Sequences Leads to Dysregulation of Matrix Metalloproteinase 19 in Patients with Cavitary Optic Disc Anomaly

2015 ◽  
Vol 36 (3) ◽  
pp. 369-378 ◽  
Author(s):  
Ralph J. Hazlewood ◽  
Benjamin R. Roos ◽  
Frances Solivan-Timpe ◽  
Robert A. Honkanen ◽  
Lee M. Jampol ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Optic Disc ◽  
Regulatory Sequences ◽  
Optic Disc Anomaly ◽  
Upstream Regulatory Sequences

High Myopia–Excavated Optic Disc Anomaly Associated With a Frameshift Mutation in the MYC-Binding Protein 2 Gene (MYCBP2)

2015 ◽  
Vol 159 (5) ◽  
pp. 973-979.e2 ◽  
Author(s):  
Cecilie Bredrup ◽  
Stefan Johansson ◽  
Laurence A. Bindoff ◽  
Pawel Sztromwasser ◽  
Jostein Kråkenes ◽  
...  
Keyword(s):  
Optic Disc ◽  
High Myopia ◽  
Frameshift Mutation ◽  
Binding Protein ◽  
Optic Disc Anomaly

Upstream regulatory sequences of the yeast RNR2 gene include a repression sequence and an activation site that binds the RAP1 protein

1989 ◽  
Vol 9 (12) ◽  
pp. 5359-5372
Author(s):  
H K Hurd ◽  
J W Roberts
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Ribonucleotide Reductase ◽  
Small Subunit ◽  
Methyl Methanesulfonate ◽  
Regulatory Sequences ◽  
Start Site ◽  
Transcription Start ◽  
Dna Damaging Agents ◽  
Number Of Genes ◽  
Upstream Regulatory Sequences

The small subunit of ribonucleotide reductase in Saccharomyces cerevisiae (RNR2) was induced 3- to 20-fold by a variety of DNA-damaging agents. Induction of the RNR2 transcript by at least one of these agents, methyl methanesulfonate, did not require protein synthesis. To identify sequences involved in the regulation of RNR2, we introduced deletions upstream of the transcription start site. Sequences required for induction were contained within a 200-base-pair region that could confer methyl methanesulfonate inducibility on the heterologous CYC1 promoter. This region contained a repression sequence and at least two positive activation sites. One of these activation sites bound RAP1, a protein known to associate with mating-type silencers and the upstream activation sequences of a number of genes. The behavior of deletions of the repression sequence suggests that induction of RNR2 may occur, at least in part, through relief of repression.

Upstream regulatory sequences from two ?-conglycinin genes

1993 ◽  
Vol 22 (5) ◽  
pp. 873-885 ◽  
Author(s):  
Philip A. Lessard ◽  
Randy D. Allen ◽  
Toru Fujiwara ◽  
Roger N. Beachy
Keyword(s):  
Regulatory Sequences ◽  
Upstream Regulatory Sequences

scholarly journals Homeostatic Regulation of Copper Uptake in Yeast via Direct Binding of MAC1 Protein to Upstream Regulatory Sequences ofFRE1andCTR1

1997 ◽  
Vol 272 (28) ◽  
pp. 17711-17718 ◽  
Author(s):  
Yuko Yamaguchi-Iwai ◽  
Mihaela Serpe ◽  
David Haile ◽  
Weimin Yang ◽  
Daniel J. Kosman ◽  
...  
Keyword(s):  
Regulatory Sequences ◽  
Homeostatic Regulation ◽  
Copper Uptake ◽  
Direct Binding ◽  
Upstream Regulatory Sequences

Identification of a Gain-of-Function SNP Causing a New Model of α-Thalassaemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 523-523
Author(s):  
Marco De Gobbi ◽  
Vip Viprakasit ◽  
Pieter J. de Jong ◽  
Yuko Yoshinaga ◽  
Jan-Fang Cheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Site ◽  
Globin Gene ◽  
Regulation Of Gene Expression ◽  
Histone H3 ◽  
Regulatory Elements ◽  
Causative Mutation ◽  
Regulatory Sequences ◽  
Chromosome 16 ◽  
Upstream Regulatory Sequences

Abstract The human α globin cluster includes an embryonic gene ζ and 2 fetal/adult genes (α2 and α1) arranged along the chromosome in the order in which they are expressed in development (5′-ζ-pseudoζ- αD- α2-α1-𝛉-3′). Fully activated expression of these genes in erythroid cells depends on upstream regulatory elements of which HS-40, located 40kb upstream of the cluster, appears to exert the greatest effect. We have recently shown that during terminal differentiation, key transcription factors (GATA-2, GATA-1, NF-E2, SCL complex) sequentially bind the α promoters and their regulatory elements and a domain of histone acetylation develops which eventually encompasses the entire α globin cluster including the upstream regulatory sequences. α-thalassemia most frequently results from deletions or point mutations affecting the structural α globin genes, but may also result from rare sporadic deletions which remove the upstream regulatory sequences. In a single family α globin expression was silenced by a mutation which drives an anti-sense RNA through the α gene. Alpha thalassemia may also result from inherited and acquired mutations in a trans-acting factor called ATRX. Over the past few years we have continued to screen for new mechanisms which lead to α thalassemia and thereby elucidate new principles underlying the regulation of gene expression in hemopoiesis. Here we describe a new mechanism of α thalassemia occurring in Pacific Islanders in whom we could detect no mutations or rearrangements in the α globin gene locus. Despite this, extensive genetic analysis showed unequivocally that the causative mutation is linked to the terminal 169kb of chromosome 16 (Viprakasit et al accompanying abstract). Analysis of globin synthesis, steady state RNA levels and detection of RNA in situ demonstrated that the mutation downregulates α globin transcription. To identify the mutation, we constructed a new BAC library from an affected homozygote, isolated and re-sequenced the candidate region and focussed further analysis on 8 SNPS within the α globin cluster, one of which creates a new GATA-1 binding site (GACA>GATA). Using primary erythroblasts from normal individuals and patients with this form of thalassemia, together with interspecific hybrids containing either the normal or abnormal copy of chromosome 16, we have shown that this SNP creates a new binding site in vivo for GATA-1 and the SCL complex. Furthermore, the chromatin at this site becomes activated as judged by acetylation of histone H3 and H4 (H3ac2 and H4ac4) and methylation of histone H3 (H3K4me2). Based on these data we postulate that an active transcriptional complex binding this new GATA site created by the SNP-mutation, could distract the upstream regulatory regions, which normally interact with the α globin promoter, and silence α globin gene expression. This model thus represents a new example of α globin gene down-regulation and a new mechanism by which gene expression can be perturbed during hemopoiesis.

Sign in / Sign up

Export Citation Format

Share Document