scholarly journals Regulation of Social Stress and Neural Degeneration by Activity-Regulated Genes and Epigenetic Mechanisms in Dopaminergic Neurons

2020 ◽  
Vol 57 (11) ◽  
pp. 4500-4510
Author(s):  
Clement Kent ◽  
Pavan Agrawal
Keyword(s):  
Transcription Factors ◽  
Neurodegenerative Disorders ◽  
Dopaminergic Neurons ◽  
Social Stress ◽  
Social Deprivation ◽  
Specific Pattern ◽  
Gene Promoters ◽  
Stress Injury ◽  
Epigenetic Marks ◽  
Small Set

Abstract Transcriptional and epigenetic regulation of both dopaminergic neurons and their accompanying glial cells is of great interest in the search for therapies for neurodegenerative disorders such as Parkinson’s disease (PD). In this review, we collate transcriptional and epigenetic changes identified in adult Drosophila melanogaster dopaminergic neurons in response to either prolonged social deprivation or social enrichment, and compare them with changes identified in mammalian dopaminergic neurons during normal development, stress, injury, and neurodegeneration. Surprisingly, a small set of activity-regulated genes (ARG) encoding transcription factors, and a specific pattern of epigenetic marks on gene promoters, are conserved in dopaminergic neurons over the long evolutionary period between mammals and insects. In addition to their classical function as immediate early genes to mark acute neuronal activity, these ARG transcription factors are repurposed in both insects and mammals to respond to chronic perturbations such as social enrichment, social stress, nerve injury, and neurodegeneration. We suggest that these ARG transcription factors and epigenetic marks may represent important targets for future therapeutic intervention strategies in various neurodegenerative disorders including PD.

scholarly journals The dorsoanterior brain of adult amphioxus shares similarities in expression profile and neuronal composition with the vertebrate telencephalon

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Èlia Benito-Gutiérrez ◽  
Giacomo Gattoni ◽  
Manuel Stemmer ◽  
Silvia D. Rohr ◽  
Laura N. Schuhmacher ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dopaminergic Neurons ◽  
Ventricular Zone ◽  
Anterior Part ◽  
Brain Regions ◽  
Specific Pattern ◽  
Vertebrate Brain ◽  
Neuronal Progenitors ◽  
Brain Parts ◽  
Combinatorial Expression

Abstract Background The evolutionary origin of the telencephalon, the most anterior part of the vertebrate brain, remains obscure. Since no obvious counterpart to the telencephalon has yet been identified in invertebrate chordates, it is difficult to trace telencephalic origins. One way to identify homologous brain parts between distantly related animal groups is to focus on the combinatorial expression of conserved regionalisation genes that specify brain regions. Results Here, we report the combined expression of conserved transcription factors known to specify the telencephalon in the vertebrates in the chordate amphioxus. Focusing on adult specimens, we detect specific co-expression of these factors in the dorsal part of the anterior brain vesicle, which we refer to as Pars anterodorsalis (PAD). As in vertebrates, expression of the transcription factors FoxG1, Emx and Lhx2/9 overlaps that of Pax4/6 dorsally and of Nkx2.1 ventrally, where we also detect expression of the Hedgehog ligand. This specific pattern of co-expression is not observed prior to metamorphosis. Similar to the vertebrate telencephalon, the amphioxus PAD is characterised by the presence of GABAergic neurons and dorsal accumulations of glutamatergic as well as dopaminergic neurons. We also observe sustained proliferation of neuronal progenitors at the ventricular zone of the amphioxus brain vesicle, as observed in the vertebrate brain. Conclusions Our findings suggest that the PAD in the adult amphioxus brain vesicle and the vertebrate telencephalon evolved from the same brain precursor region in ancestral chordates, which would imply homology of these structures. Our comparative data also indicate that this ancestral brain already contained GABA-, glutamatergic and dopaminergic neurons, as is characteristic for the olfactory bulb of the vertebrate telencephalon. We further speculate that the telencephalon might have evolved in vertebrates via a heterochronic shift in developmental timing.

scholarly journals PINK1 deficiency impairs adult neurogenesis of dopaminergic neurons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sarah J. Brown ◽  
Ibrahim Boussaad ◽  
Javier Jarazo ◽  
Julia C. Fitzgerald ◽  
Paul Antony ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Neurodegenerative Disorders ◽  
Dopaminergic Neurons ◽  
Adult Life ◽  
Lineage Tracing ◽  
Model Systems ◽  
Wild Type ◽  
Therapeutic Approaches ◽  
Early Effect ◽  
Early Adult Life

AbstractRecent evidence suggests neurogenesis is on-going throughout life but the relevance of these findings for neurodegenerative disorders such as Parkinson’s disease (PD) is poorly understood. Biallelic PINK1 mutations cause early onset, Mendelian inherited PD. We studied the effect of PINK1 deficiency on adult neurogenesis of dopaminergic (DA) neurons in two complementary model systems. Zebrafish are a widely-used model to study neurogenesis in development and through adulthood. Using EdU analyses and lineage-tracing studies, we first demonstrate that a subset of ascending DA neurons and adjacent local-projecting DA neurons are each generated into adulthood in wild type zebrafish at a rate that decreases with age. Pink1-deficiency impedes DA neurogenesis in these populations, most significantly in early adult life. Pink1 already exerts an early effect on Th1+ progenitor cells rather than on differentiated DA neurons only. In addition, we investigate the effect of PINK1 deficiency in a human isogenic organoid model. Global neuronal differentiation in PINK1-deficient organoids and isogenic controls is similar, but PINK1-deficient organoids display impeded DA neurogenesis. The observation of impaired adult dopaminergic neurogenesis in Pink1 deficiency in two complementing model systems may have significant consequences for future therapeutic approaches in human PD patients with biallelic PINK1 mutations.

scholarly journals Differential regulation of neuronal nicotinic acetylcholine receptor subunit gene promoters by Brn-3 POU family transcription factors

1996 ◽  
Vol 317 (2) ◽  
pp. 419-423 ◽  
Author(s):  
Nathaniel G. N. MILTON ◽  
Alain BESSIS ◽  
Jean-Pierre CHANGEUX ◽  
David S. LATCHMAN
Keyword(s):  
Transcription Factors ◽  
Regulatory Region ◽  
Differential Regulation ◽  
Gene Promoters ◽  
The Novel ◽  
Receptor Subunit ◽  
Subunit Gene ◽  
Related Factors ◽  
Nicotinic Acetylcholine ◽  
Stimulation Of

The regulatory region of the neuronal nicotinic acetylcholine (nACh) receptor α2 subunit gene is activated by the Brn-3b POU family transcription factor but not by the closely related factors Brn-3a and Brn-3c. This pattern of regulation has not previously been observed for other neuronally expressed genes, several of which, such as those encoding α-internexin or SNAP-25, are activated by Brn-3a and Brn-3c but repressed by Brn-3b. The α3 nACh receptor subunit gene is also shown to be activated by Brn-3a but is repressed by Brn-3b and Brn-3c. In contrast, the Brn-3 POU family transcription factors have no effects on either the α7 or β4 nACh receptor subunit genes. The actions of Brn-3b on the α2 subunit are thus in contrast to the inhibitory actions of Brn-3b on several promoters that are activated by Brn-3a. The different actions of the Brn-3 POU factors on the range of nACh receptor genes tested suggests that the novel stimulation of the α2 subunit by Brn-3b is specific to this subunit and not a general feature of nACh receptor genes.

scholarly journals HOT or not: examining the basis of high-occupancy target regions

2017 ◽  
Author(s):  
Katarzyna Wreczycka ◽  
Vedran Franke ◽  
Bora Uyar ◽  
Ricardo Wurmus ◽  
Altuna Akalin
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Cell Types ◽  
Data Sets ◽  
Gene Promoters ◽  
Quadruplex Dna ◽  
Golden Standard ◽  
Multiple Cell ◽  
Multiple Species

AbstractHigh-occupancy target (HOT) regions are the segments of the genome with unusually high number of transcription factor binding sites. These regions are observed in multiple species and thought to have biological importance due to high transcription factor occupancy. Furthermore, they coincide with house-keeping gene promoters and the associated genes are stably expressed across multiple cell types. Despite these features, HOT regions are solemnly defined using ChIP-seq experiments and shown to lack canonical motifs for transcription factors that are thought to be bound there. Although, ChIP-seq experiments are the golden standard for finding genome-wide binding sites of a protein, they are not noise free. Here, we show that HOT regions are likely to be ChIP-seq artifacts and they are similar to previously proposed “hyper-ChIPable” regions. Using ChIP-seq data sets for knocked-out transcription factors, we demonstrate presence of false positive signals on HOT regions. We observe sequence characteristics and genomic features that are discriminatory of HOT regions, such as GC/CpG-rich k-mers and enrichment of RNA-DNA hybrids (R-loops) and DNA tertiary structures (G-quadruplex DNA). The artificial ChIP-seq enrichment on HOT regions could be associated to these discriminatory features. Furthermore, we propose strategies to deal with such artifacts for the future ChIP-seq studies.

scholarly journals hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors.

1993 ◽  
Vol 13 (4) ◽  
pp. 2564-2577 ◽  
Author(s):  
J C McDermott ◽  
M C Cardoso ◽  
Y T Yu ◽  
V Andres ◽  
D Leifer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Cortical Neurons ◽  
Myogenic Differentiation ◽  
Mrna Level ◽  
Functional Characterization ◽  
Essential Element ◽  
Specific Pattern ◽  
Cdna Clones ◽  
Tissue Specific

The myocyte enhancer-binding factor 2 (MEF2) site is an essential element of many muscle-specific enhancers and promoters that binds nuclear proteins from muscle and brain. Recently, we have cloned a family of MEF2 transcription factors produced by two genes that, at the mRNA level, are broadly expressed and produce tissue-specific isoforms by posttranscriptional processes (Y.-T. Yu, R. E. Breitbart, L. B. Smoot, Y. Lee, V. Mahdavi, and B. Nadal-Ginard, Genes Dev. 6:1783-1798, 1992). Here, we report the isolation and functional characterization of cDNA clones encoding four MEF2 factors derived from a separate gene that we have named hMEF2C. In contrast to those of the previously reported genes, the transcripts of the hMEF2C gene are restricted to skeletal muscle and brain. One of the alternate exons is exclusively present in brain transcripts. The products of this gene have DNA-binding and trans-activating activities indistinguishable from those of the previously reported MEF2 factors. The hMEF2C gene is induced late during myogenic differentiation, and its expression is limited to a subset of cortical neurons. The potential targets for this transcription factor in a subset of neurons are not known at this time. The strict tissue-specific pattern of expression of hMEF2C in comparison with the more ubiquitous expression of other MEF2 genes suggests a different mode of regulation and a potentially important role of hMEF2C factors in myogenesis and neurogenesis.

scholarly journals Identification of two factors required for transcription of the ovalbumin gene.

1986 ◽  
Vol 6 (12) ◽  
pp. 4259-4267 ◽  
Author(s):  
I Sagami ◽  
S Y Tsai ◽  
H Wang ◽  
M J Tsai ◽  
B W O'Malley
Keyword(s):  
Molecular Weight ◽  
Transcription Factors ◽  
Gradient Centrifugation ◽  
Globin Gene ◽  
Sodium Dodecyl ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Gene Promoters ◽  
Early Genes

Two transcription factors, COUP and S300-II, were isolated and partially purified from HeLa cell nuclear extracts. Both factors are required for the efficient transcription in vitro of the ovalbumin gene but not the simian virus 40 early genes. COUP factor binds to the chicken ovalbumin upstream promoter (COUP) sequence which lies between -70 to -90 base pairs upstream from the cap site. A series of competition experiments with a band-shifting assay was carried out to determine the relative affinity of COUP box transcription factor for various promoters. We found that a promoter DNA fragment isolated from the ovalbumin gene competes better than those isolated from the ovomucoid, Y, and alpha-genes. In contrast, the the simian virus 40 early genes, the beta-globin gene, and the adenosine deaminase gene promoters do not compete well in this assay. The molecular weight of the COUP factor was estimated by S-300 column chromatography, glycerol gradient centrifugation to be 90,000. However, two bands were observed in sodium dodecyl sulfate gel electrophoresis of cross-linked COUP factor to a 32P-labeled oligonucleotide containing the COUP sequence. The protein moieties of the major and minor bands were estimated to be 85,000 to 90,000 and 40,000 to 45,000, respectively. The S300-II factor with an apparent molecular weight of 45,000 in an S-300 column is required for function in an in vitro reconstituted transcription system. In contrast to the COUP factor, the S300-II factor does not have apparent specificity for binding to the ovalbumin gene promoter. The S300-II factor may function by interacting with RNA polymerase or other DNA-binding transcription factors.

scholarly journals Genome-wide identification and expression analysis of bZIP gene family in Carthamus tinctorius L.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Haoyang Li ◽  
Lixia Li ◽  
Guodong ShangGuan ◽  
Chang Jia ◽  
Sinan Deng ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Functional Characterization ◽  
Draft Genome ◽  
Functional Differentiation ◽  
Regulatory Elements ◽  
Carthamus Tinctorius ◽  
Specific Pattern ◽  
Basic Leucine Zipper ◽  
Protein Motifs ◽  
Genome Wide

Abstract The basic leucine zipper (bZIP) is a widely known transcription factors family in eukaryotes. In plants, the role of bZIP proteins are crucial in various biological functions such as plant growth and development, seed maturation, response to light signal and environmental stress. To date, bZIP protein family has been comprehensively identified in Arabidopsis, castor, rice, ramie, soybean and other plant species, however, the complete genome-wide investigation of Carthamus tinctorius-bZIP family still remains unexplained. Here, we identified 52 putative bZIP genes from Carthamus tinctorius using a draft genome assembly and further analyzed their evolutionary classification, physicochemical properties, Conserved domain analysis, functional differentiation and the investigation of expression level in different tissues. Based on the common bZIP domain, CtbZIP family were clustered into 12 subfamilies renamed as (A–J, S, X), of which the X is a unique subfamily to Carthamus tinctorius. A total of 20 conserved protein motifs were found in CtbZIP proteins. The expression profiling of CtbZIP genes deciphered their tissue-specific pattern. Furthermore, the changes in CtbZIP transcript abundance suggested that their transcription regulation could be highly influenced by light intensity and hormones. Collectively, this study highlights all functional and regulatory elements of bZIP transcription factors family in Carthamus tinctorius which may serve as potential candidates for functional characterization in future.

Activation domains of gene-specific transcription factors: are histones among their targets?

2004 ◽  
Vol 82 (4) ◽  
pp. 453-459 ◽  
Author(s):  
Alexandre M Erkine
Keyword(s):  
Transcription Factors ◽  
Amino Acid ◽  
Chromatin Remodeling ◽  
Transcription Initiation ◽  
Protein Complexes ◽  
Amino Acid Sequences ◽  
Gene Promoters ◽  
Activation Domain ◽  
Activation Domains ◽  
Multiple Protein

Activation domains of promoter-specific transcription factors are critical entities involved in recruitment of multiple protein complexes to gene promoters. The activation domains often retain functionality when transferred between very diverse eukaryotic phyla, yet the amino acid sequences of activation domains do not bear any specific consensus or secondary structure. Activation domains function in the context of chromatin structure and are critical for chromatin remodeling, which is associated with transcription initiation. The mechanisms of direct and indirect recruitment of chromatin-remodeling and histone-modifying complexes, including mechanisms involving direct interactions between activation domains and histones, are discussed.Key words: activation domain, transcription, chromatin, nucleosome.

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