Regulation of gene expression via the core promoter and the basal transcriptional machinery

The target of rapamycin (TOR) protein kinase is at the core of growth factor- and nutrient-dependent signaling pathways that are well-known for their regulation of metabolism, growth, and proliferation. However, TOR is also involved in the regulation of gene expression, genomic and epigenomic stability. TOR affects nuclear functions indirectly through its activity in the cytoplasm, but also directly through active nuclear TOR pools. The mechanisms by which TOR regulates its nuclear functions are less well-understood compared with its cytoplasmic activities. TOR is an important pharmacological target for several diseases, including cancer, metabolic and neurological disorders. Thus, studies of the nuclear functions of TOR are important for our understanding of basic biological processes, as well as for clinical implications.

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Molecular characterization of the ACSS2 gene involved in adaptation to hypoxia in high-altitude cattle breeds

Animal Biology ◽

10.1163/15707563-bja10046 ◽

2020 ◽

Vol 71 (1) ◽

pp. 49-66

Author(s):

Han Zhao ◽

Yaping Gao ◽

Qiang Jiang ◽

Jinpeng Wang ◽

Wenhao Liu ◽

...

Keyword(s):

Gene Expression ◽

High Altitude ◽

Bos Taurus ◽

Luciferase Activity ◽

Core Promoter ◽

Acetyl Coa ◽

Altitude Hypoxia ◽

The Core ◽

Cattle Breeds ◽

Bos Taurus Indicus

Abstract Under extreme environmental conditions such as hypoxia, insufficient nutrition, and glucose deficiency, the acetyl-CoA synthetase 2 (ACSS2)-mediated acetyl-CoA synthesis pathway plays an alternative role to ensure the normal operation of metabolic activities. To investigate the potential effect of the ACSS2 gene on hypoxic adaptation and its regulatory mechanism of gene expression in high-altitude cattle breeds, we analyzed the genetic variations of the ACSS2 gene in five Bos taurus taurus, Bos taurus indicus, hybrid Bos taurus taurus × Bos taurus indicus Chinese cattle breeds, and two Bos grunniens (yak) breeds distributed at different altitudes (95-3850 m). A total of 58 SNPs was detected in seven populations, and abundant genetic variation was found in high-altitude breeds. We identified the bovine ACSS2 core promoter region between g.-682 and g.-264 by using the luciferase assay in FFB and HepG2 cells. We also identified that the high-altitude hypoxia-specific haplotype (CAGTCT) was composed of six highly linked SNPs. The tagSNP g.-473 T>C (rs23) is located in the core promoter of ACSS2 in the Bos taurus taurus and yak breeds. The recombinant plasmid containing rs23 and analyses of luciferase activity of different genotypes showed that the activity of ACSS2 promoter increased significantly when T was mutated to C. We also found a yak-specific SNP rs20 that consists of 12 base insertions (g.-562 ins GAAAGGACCCTA) in the promoter of yak breeds. Luciferase activity analysis showed that the insertion mutant significantly decreased the promoter activity of ACSS2. Hence, ACSS2 may play an important role in the adaptation to high-altitude hypoxia by generating adaptive alleles to influence gene transcription in cattle. These results signify that different genetic variants and haplotypes affect the activity of the core promoter to regulate ACSS2 gene expression and subsequently overcome and adapt to a high-altitude environment within different cattle breeds. Our findings may have important implications for understanding the mechanism of adaptation to high altitude and for application of molecular breeding in Bos species.

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The Core Promoter Is a Regulatory Hub for Developmental Gene Expression

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.666508 ◽

2021 ◽

Vol 9 ◽

Author(s):

Anna Sloutskin ◽

Hila Shir-Shapira ◽

Richard N. Freiman ◽

Tamar Juven-Gershon

Keyword(s):

Gene Expression ◽

Transcriptional Activation ◽

Transcription Initiation ◽

Promoter Region ◽

Core Promoter ◽

Developmental Gene ◽

Core Promoter Region ◽

Developmental Gene Expression ◽

The Core ◽

Regulatory Module

The development of multicellular organisms and the uniqueness of each cell are achieved by distinct transcriptional programs. Multiple processes that regulate gene expression converge at the core promoter region, an 80 bp region that directs accurate transcription initiation by RNA polymerase II (Pol II). In recent years, it has become apparent that the core promoter region is not a passive DNA component, but rather an active regulatory module of transcriptional programs. Distinct core promoter compositions were demonstrated to result in different transcriptional outputs. In this mini-review, we focus on the role of the core promoter, particularly its downstream region, as the regulatory hub for developmental genes. The downstream core promoter element (DPE) was implicated in the control of evolutionarily conserved developmental gene regulatory networks (GRNs) governing body plan in both the anterior-posterior and dorsal-ventral axes. Notably, the composition of the basal transcription machinery is not universal, but rather promoter-dependent, highlighting the importance of specialized transcription complexes and their core promoter target sequences as key hubs that drive embryonic development, differentiation and morphogenesis across metazoan species. The extent of transcriptional activation by a specific enhancer is dependent on its compatibility with the relevant core promoter. The core promoter content also regulates transcription burst size. Overall, while for many years it was thought that the specificity of gene expression is primarily determined by enhancers, it is now clear that the core promoter region comprises an important regulatory module in the intricate networks of developmental gene expression.

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Control of human gene expression: High abundance of divergent transcription in genes containing both INR and BRE elements in the core promoter

PLoS ONE ◽

10.1371/journal.pone.0202927 ◽

2018 ◽

Vol 13 (8) ◽

pp. e0202927 ◽

Cited By ~ 2

Author(s):

Jay C. Brown

Keyword(s):

Gene Expression ◽

Human Gene ◽

Core Promoter ◽

High Abundance ◽

Human Gene Expression ◽

The Core ◽

Divergent Transcription

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Endothelial-cell-specific regulation of von Willebrand factor gene expression

Molecular and Cellular Biology ◽

10.1128/mcb.14.2.999-1008.1994 ◽

1994 ◽

Vol 14 (2) ◽

pp. 999-1008

Author(s):

N Jahroudi ◽

D C Lynch

Keyword(s):

Gene Expression ◽

Endothelial Cell ◽

Core Promoter ◽

Regulatory Element ◽

Regulatory Region ◽

Specific Gene ◽

Cell Type ◽

The Core ◽

Cell Type Specific ◽

Von Willebrand

In both tissue sections and cell culture, the endothelial nature of a cell is most commonly determined by demonstration of its expression of von Willebrand factor (vWf) protein and/or mRNA. Thus, the mechanism of cell-type-specific transcriptional regulation of the vWf gene is central to studying the basis of endothelial-cell-specific gene expression. In this study, deletion analyses were carried out to identify the region of the vWf gene which regulates its endothelial-cell-specific expression. A 734-bp fragment which spans the sequence from -487 to +247 relative to the transcription start site was identified as the cell-type-specific promoter. It consists of a minimal core promoter located between -90 and +22, a strong negative regulatory element located upstream of the core promoter (ca. -500 to -300), and a positive regulatory region located downstream of the core promoter in the first exon. The activity of the core promoter is not cell type specific, and the negative regulatory region is required to inhibit its activity in all cell types. The positive regulatory region relieves this inhibition only in endothelial cells and results in endothelial-cell-specific gene expression. The positive regulatory region contains sequences predicting possible SP1, GATA, and octamer binding sites. Mutations in either the SP1 or octamer sequence have no effect on transcriptional activity, while mutation in the GATA binding element totally abolishes the promoter activity. Evidence that a GATA factor is involved in this interaction is presented. Thus, the positive regulatory region with an intact GATA binding site is required to overcome the inhibitory effect of the negative regulatory element and activate vWf gene expression in an endothelial-cell-specific manner.

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The RNA polymerase II core promoter: a key component in the regulation of gene expression

Genes & Development ◽

10.1101/gad.1026202 ◽

2002 ◽

Vol 16 (20) ◽

pp. 2583-2592 ◽

Cited By ~ 374

Author(s):

J. E.F. Butler

Keyword(s):

Gene Expression ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Core Promoter ◽

Regulation Of Gene Expression

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Regulation of gene expression in the protozoan parasite Entamoeba invadens: identification of core promoter elements and promoters with stage-specific expression patterns

International Journal for Parasitology ◽

10.1016/j.ijpara.2014.06.008 ◽

2014 ◽

Vol 44 (11) ◽

pp. 837-845 ◽

Cited By ~ 7

Author(s):

Dipak Manna ◽

Gretchen M. Ehrenkaufer ◽

Upinder Singh

Keyword(s):

Gene Expression ◽

Core Promoter ◽

Expression Patterns ◽

Regulation Of Gene Expression ◽

Protozoan Parasite ◽

Promoter Elements ◽

Specific Expression ◽

Entamoeba Invadens

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Nascent RNA sequencing reveals distinct features in plant transcription

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1603217113 ◽

2016 ◽

Vol 113 (43) ◽

pp. 12316-12321 ◽

Cited By ~ 52

Author(s):

Jonathan Hetzel ◽

Sascha H. Duttke ◽

Christopher Benner ◽

Joanne Chory

Keyword(s):

Gene Expression ◽

Steady State ◽

De Novo ◽

Core Promoter ◽

Regulation Of Gene Expression ◽

Rna Polymerases ◽

Major Mechanism ◽

Eukaryotic Gene ◽

Nascent Transcripts ◽

Distinct Features

Transcriptional regulation of gene expression is a major mechanism used by plants to confer phenotypic plasticity, and yet compared with other eukaryotes or bacteria, little is known about the design principles. We generated an extensive catalog of nascent and steady-state transcripts inArabidopsis thalianaseedlings using global nuclear run-on sequencing (GRO-seq), 5′GRO-seq, and RNA-seq and reanalyzed published maize data to capture characteristics of plant transcription. De novo annotation of nascent transcripts accurately mapped start sites and unstable transcripts. Examining the promoters of coding and noncoding transcripts identified comparable chromatin signatures, a conserved “TGT” core promoter motif and unreported transcription factor-binding sites. Mapping of engaged RNA polymerases showed a lack of enhancer RNAs, promoter-proximal pausing, and divergent transcription inArabidopsisseedlings and maize, which are commonly present in yeast and humans. In contrast,Arabidopsisand maize genes accumulate RNA polymerases in proximity of the polyadenylation site, a trend that coincided with longer genes and CpG hypomethylation. Lack of promoter-proximal pausing and a higher correlation of nascent and steady-state transcripts indicateArabidopsismay regulate transcription predominantly at the level of initiation. Our findings provide insight into plant transcription and eukaryotic gene expression as a whole.

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