scholarly journals Altered gene regulation and synaptic morphology in Drosophila learning and memory mutants

2011 ◽  
Vol 18 (4) ◽  
pp. 191-206 ◽  
Author(s):  
Z. Guan ◽  
L. K. Buhl ◽  
W. G. Quinn ◽  
J. T. Littleton
Keyword(s):  
Gene Regulation ◽  
Learning And Memory ◽  
Memory Mutants ◽  
Altered Gene

Altered Expression of Transcription and Chromatin Remodeling Factors in Deletional HPFH.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2705-2705
Author(s):  
Fernando F. Costa ◽  
Tiago G. de Andrade ◽  
Anderson F. Cunha ◽  
André Fattori ◽  
Sara T.O. Saad
Keyword(s):  
Gene Regulation ◽  
Chromatin Remodeling ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Subtractive Hybridization ◽  
Cdna Libraries ◽  
Altered Expression ◽  
Hereditary Disorders ◽  
Altered Gene ◽  
Globin Gene Regulation

Abstract Hereditary Persistence of Fetal Hemoglobin is a rare, heterogeneous and benign group of hereditary disorders with an abnormal switch from fetal to adult hemoglobin, resulting in high levels of Hb F in the adult stage. A total of six deletions related to HPFH have been described, associated with increased levels of both gamma chains. Three main hypotheses have been proposed to explain the relationship between these deletions and the non-suppression of gamma genes: the removal of competitive regions that interact with the LCR; the juxtaposition of enhancer elements; and the removal of silencers. Despite evidence to support these hypotheses, however, they are not conclusive. Recently, Xiang and cols (Abstract #1215, 2004 ASH Meeting; Blood, Volume 104, issue 11, November 16, 2004) developed a YAC construct with the whole beta-globin locus containing a deletion of approximately 83.5 Kb responsible for the HPFH-2. Unexpectedly, the gamma gene was completely silenced in the adult transgenic mice. These data suggest that other mechanisms could be involved in the increased levels of HbF in these conditions. The authors speculate that other regions upstream from the cluster may harbor this activity. We, herein, investigate the possible involvement of transcription factors, using the subtractive hybridization method to identify differentially expressed transcripts in reticulocytes from a normal subject and a HPFH-2 subject. We have identified 56 and 106 unique genes in the normal and HPFH-2 cDNA libraries, respectively. Some of these are transcription (zinc fingers and homeobox proteins) and chromatin remodeling (NAP and SWI like proteins) factors that could participate in globin gene regulation. These genes are located in cis or in trans to the deletion and their altered gene expression has been confirmed by Quantitative Real-time PCR in other two HPFH subjects. The data may present new clues about globin gene regulation, the increased expression of gamma gene in deletional HPFH and the dynamic organization of genes and chromosomes in cells.

scholarly journals Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation

Blood ◽  
2005 ◽  
Vol 106 (1) ◽  
pp. 304-310 ◽  
Author(s):  
Wen-Chien Chou ◽  
Hsuan-Yu Chen ◽  
Sung-Liang Yu ◽  
Linzhao Cheng ◽  
Pan-Chyr Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Prolonged Exposure ◽  
Promyelocytic Leukemia ◽  
Microarray Gene Expression ◽  
Sp1 Transcription Factor ◽  
Ros Scavenger ◽  
Microarray Gene Expression Analysis ◽  
Altered Gene

The mechanism by which arsenic dramatically affects gene expression remains poorly understood. Here we report that prolonged exposure of acute promyelocytic leukemia NB4 cells to low levels of arsenic trioxide increased the expression of a set of genes responsible for reactive oxygen species (ROS) production. We hypothesize that arsenic-induced ROS in turn contribute partially to altered gene expression. To identify genes responsive to arsenic-induced ROS, we used microarray gene expression analysis and identified genes that responded to arsenic and hydrogen peroxide but whose response to arsenic was reversed by an ROS scavenger, N-acetyl-L-cysteine. We found that 26% of the genes significantly responsive to arsenic might have been directly altered by ROS. We further explored the mechanisms by which ROS affects gene regulation and found that the Sp1 transcription factor was oxidized by arsenic treatment, with a corresponding decrease in its in situ binding on the promoters of 3 genes, hTERT, C17, and c-Myc, whose expressions were significantly suppressed. We conclude that ROS contributed partly to arsenic-mediated gene regulation and that Sp1 oxidation contributed to gene suppression by arsenic-induced ROS.

Altered gene regulation as a candidate mechanism by which ciliopathy gene SDCCAG8 contributes to schizophrenia and cognitive function

2019 ◽  
Vol 29 (3) ◽  
pp. 407-417
Author(s):  
Mairéad Flynn ◽  
Laura Whitton ◽  
Gary Donohoe ◽  
Ciaran G Morrison ◽  
Derek W Morris
Keyword(s):  
Gene Regulation ◽  
Association Studies ◽  
Cell Signalling ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Phenotypic Analysis ◽  
Genome Wide ◽  
Dependent Cell ◽  
Altered Gene

Abstract Mutations in genes that encode centrosomal/ciliary proteins cause severe cognitive deficits, while common single-nucleotide polymorphisms in these genes are associated with schizophrenia (SZ) and cognition in genome-wide association studies. The role of these genes in neuropsychiatric disorders is unknown. The ciliopathy gene SDCCAG8 is associated with SZ and educational attainment (EA). Genome editing of SDCCAG8 caused defects in primary ciliogenesis and cilium-dependent cell signalling. Transcriptomic analysis of SDCCAG8-deficient cells identified differentially expressed genes that are enriched in neurodevelopmental processes such as generation of neurons and synapse organization. These processes are enriched for genes associated with SZ, human intelligence (IQ) and EA. Phenotypic analysis of SDCCAG8-deficent neuronal cells revealed impaired migration and neuronal differentiation. These data implicate ciliary signalling in the aetiology of SZ and cognitive dysfunction. We found that centrosomal/ciliary genes are enriched for association with IQ, suggesting altered gene regulation as a general model for neurodevelopmental impacts of centrosomal/ciliary genes.

Modifiable, Non-Modifiable, and Clinical Factors Associated with Progression of Alzheimer’s Disease

2021 ◽  
pp. 1-27
Author(s):  
David A. Loeffler
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Regulation ◽  
Genetic Variants ◽  
Neuropsychiatric Symptoms ◽  
Cognitive Level ◽  
Factors Associated ◽  
Modifiable Factors ◽  
Extrapyramidal Signs ◽  
Altered Gene

There is an extensive literature relating to factors associated with the development of Alzheimer’s disease (AD), but less is known about factors which may contribute to its progression. This review examined the literature with regard to 15 factors which were suggested by PubMed search to be positively associated with the cognitive and/or neuropathological progression of AD. The factors were grouped as potentially modifiable (vascular risk factors, comorbidities, malnutrition, educational level, inflammation, and oxidative stress), non-modifiable (age at clinical onset, family history of dementia, gender, Apolipoprotein E ɛ4, genetic variants, and altered gene regulation), and clinical (baseline cognitive level, neuropsychiatric symptoms, and extrapyramidal signs). Although conflicting results were found for the majority of factors, a positive association was found in nearly all studies which investigated the relationship of six factors to AD progression: malnutrition, genetic variants, altered gene regulation, baseline cognitive level, neuropsychiatric symptoms, and extrapyramidal signs. Whether these or other factors which have been suggested to be associated with AD progression actually influence the rate of decline of AD patients is unclear. Therapeutic approaches which include addressing of modifiable factors associated with AD progression should be considered.

scholarly journals A Multistage Sequencing Strategy Pinpoints Many Novel and Candidate Disease Alleles for Orphan Disease Emery-Dreifuss Muscular Dystrophy and Supports Gene Misregulation as its Pathomechanism

2019 ◽  
Author(s):  
Peter Meinke ◽  
Alastair R. W. Kerr ◽  
Rafal Czapiewski ◽  
Jose I. de las Heras ◽  
Elizabeth Harris ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Plasma Membrane ◽  
Muscular Dystrophy ◽  
Muscular Dystrophies ◽  
Orphan Diseases ◽  
New Approach ◽  
Genome Wide ◽  
Sequencing Strategy ◽  
Strong Candidate ◽  
Altered Gene

AbstractLimitations of genome-wide approaches for genetically-heterogenous orphan diseases led us to develop a new approach to identify novel Emery-Dreifuss muscular dystrophy (EDMD) candidate genes. We generated a primer library to genes: (I) linked to EDMD, (II) mutated in related muscular dystrophies, (III) highlighted from limited exome sequencing, (IV) encoding muscle-specific nuclear membrane proteins. Sequencing 56 unlinked EDMD patients yielded confirmed or strong candidate alleles from all categories, accounting for most remaining unlinked patients. Known functions of newly-linked genes argue the EDMD pathomechanism is from altered gene regulation and mechanotransduction through connectivity of candidates from the nuclear envelope to the plasma membrane.

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