scholarly journals BET inhibition disrupts transcription but retains enhancer-promoter contact

2019 ◽  
Author(s):  
Nicholas T. Crump ◽  
Erica Ballabio ◽  
Laura Godfrey ◽  
Ross Thorne ◽  
Emmanouela Repapi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Strong Impact ◽  
Multiple Systems ◽  
Multiple Loci ◽  
Activation Of Transcription ◽  
Mediator Protein ◽  
Enhancer Function ◽  
Specific Regulation ◽  
Increase Gene Expression

SummaryIn higher eukaryotes, enhancers are DNA sequences that enable complex temporal and tissue-specific regulation of genes. Although it is not entirely clear how enhancer-promoter interactions can increase gene expression, this proximity has been observed in multiple systems at multiple loci and is thought to be essential for the maintenance of gene expression. The formation of phase condensates is thought to be an essential component of enhancer function. Here, we show that pharmacological targeting of cells with inhibitors of BET (Bromodomain and Extra-Terminal domain) proteins can have a strong impact on transcription but very little impact on enhancer-promoter interactions. Treatment with 1,6-hexanediol, which dissolves phase condensate structures and reduces BET and Mediator protein binding at enhancers, can also have a strong effect on gene transcription, without disrupting enhancer-promoter interactions. These results suggest that activation of transcription and maintenance of enhancer-promoter interactions are separable events. Our findings further suggest that enhancer-promoter interactions are not dependent on high levels of BRD4 (Bromodomain-containing protein 4) and Mediator, and are likely maintained by a complex set of factors including additional activator complexes and loop extrusion by CTCF/cohesin.

Cell-specific regulation of IRS-1 gene expression: role of E box and C/EBP binding site in HepG2 cells and CHO cells

Diabetes ◽  
1997 ◽  
Vol 46 (3) ◽  
pp. 354-362 ◽  
Author(s):  
K. Matsuda ◽  
E. Araki ◽  
R. Yoshimura ◽  
K. Tsuruzoe ◽  
N. Furukawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Site ◽  
Cho Cells ◽  
Hepg2 Cells ◽  
E Box ◽  
Specific Regulation

Sequence-Based Deep Learning Frameworks on Enhancer-Promoter Interactions Prediction

2020 ◽  
Vol 26 ◽  
Author(s):  
Xiaoping Min ◽  
Fengqing Lu ◽  
Chunyan Li
Keyword(s):  
Gene Expression ◽  
Deep Learning ◽  
Dna Sequences ◽  
Experimental Methods ◽  
Learning Methods ◽  
Comprehensive Review ◽  
Genomic Features ◽  
Disease Mechanisms ◽  
Evaluation Strategies ◽  
Learning Frameworks

: Enhancer-promoter interactions (EPIs) in the human genome are of great significance to transcriptional regulation which tightly controls gene expression. Identification of EPIs can help us better deciphering gene regulation and understanding disease mechanisms. However, experimental methods to identify EPIs are constrained by the fund, time and manpower while computational methods using DNA sequences and genomic features are viable alternatives. Deep learning methods have shown promising prospects in classification and efforts that have been utilized to identify EPIs. In this survey, we specifically focus on sequence-based deep learning methods and conduct a comprehensive review of the literatures of them. We first briefly introduce existing sequence-based frameworks on EPIs prediction and their technique details. After that, we elaborate on the dataset, pre-processing means and evaluation strategies. Finally, we discuss the challenges these methods are confronted with and suggest several future opportunities.

A Review on Important Histone Acetyltransferase (HAT) Enzymes as Targets for Cancer Therapy

2019 ◽  
Vol 15 (2) ◽  
pp. 120-130
Author(s):  
Mohammad Ghanbari ◽  
Reza Safaralizadeh ◽  
Kiyanoush Mohammadi
Keyword(s):  
Gene Expression ◽  
Histone Acetyltransferase ◽  
Critical Role ◽  
Cancer Treatments ◽  
Control Of Gene Expression ◽  
Post Translational Modifications ◽  
Therapeutic Drugs ◽  
The Status ◽  
Acetyl Group ◽  
Increase Gene Expression

At the present time, cancer is one of the most lethal diseases worldwide. There are various factors involved in the development of cancer, including genetic factors, lifestyle, nutrition, and so on. Recent studies have shown that epigenetic factors have a critical role in the initiation and development of tumors. The histone post-translational modifications (PTMs) such as acetylation, methylation, phosphorylation, and other PTMs are important mechanisms that regulate the status of chromatin structure and this regulation leads to the control of gene expression. The histone acetylation is conducted by histone acetyltransferase enzymes (HATs), which are involved in transferring an acetyl group to conserved lysine amino acids of histones and consequently increase gene expression. On the basis of similarity in catalytic domains of HATs, these enzymes are divided into different groups such as families of GNAT, MYST, P300/CBP, SRC/P160, and so on. These enzymes have effective roles in apoptosis, signaling pathways, metastasis, cell cycle, DNA repair and other related mechanisms deregulated in cancer. Abnormal activation of HATs leads to uncontrolled amplification of cells and incidence of malignancy signs. This indicates that HAT might be an important target for effective cancer treatments, and hence there would be a need for further studies and designing of therapeutic drugs on this basis. In this study, we have reviewed the important roles of HATs in different human malignancies.

scholarly journals Bayes Estimation of Species Divergence Times and Ancestral Population Sizes Using DNA Sequences From Multiple Loci

Genetics ◽  
2003 ◽  
Vol 164 (4) ◽  
pp. 1645-1656 ◽  
Author(s):  
Bruce Rannala ◽  
Ziheng Yang
Keyword(s):  
Dna Sequences ◽  
Gene Tree ◽  
Species Tree ◽  
Bayes Estimation ◽  
Ancestral Population ◽  
Divergence Times ◽  
Gene Trees ◽  
Species Divergence ◽  
Multiple Loci ◽  
Population Sizes

Abstract The effective population sizes of ancestral as well as modern species are important parameters in models of population genetics and human evolution. The commonly used method for estimating ancestral population sizes, based on counting mismatches between the species tree and the inferred gene trees, is highly biased as it ignores uncertainties in gene tree reconstruction. In this article, we develop a Bayes method for simultaneous estimation of the species divergence times and current and ancestral population sizes. The method uses DNA sequence data from multiple loci and extracts information about conflicts among gene tree topologies and coalescent times to estimate ancestral population sizes. The topology of the species tree is assumed known. A Markov chain Monte Carlo algorithm is implemented to integrate over uncertain gene trees and branch lengths (or coalescence times) at each locus as well as species divergence times. The method can handle any species tree and allows different numbers of sequences at different loci. We apply the method to published noncoding DNA sequences from the human and the great apes. There are strong correlations between posterior estimates of speciation times and ancestral population sizes. With the use of an informative prior for the human-chimpanzee divergence date, the population size of the common ancestor of the two species is estimated to be ∼20,000, with a 95% credibility interval (8000, 40,000). Our estimates, however, are affected by model assumptions as well as data quality. We suggest that reliable estimates have yet to await more data and more realistic models.

scholarly journals The role of epigenetic modifications, long-range contacts, enhancers and topologically associating domains in the regulation of glioma grade-specific genes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ilona E. Grabowicz ◽  
Bartek Wilczyński ◽  
Bożena Kamińska ◽  
Adria-Jaume Roura ◽  
Bartosz Wojtaś ◽  
...  
Keyword(s):  
Gene Expression ◽  
Long Range ◽  
Genetic Alterations ◽  
Chromatin Organization ◽  
Open Chromatin ◽  
Low Grade ◽  
Strong Impact ◽  
Cell Matrix ◽  
Topologically Associating Domains ◽  
Genome Wide

AbstractGenome-wide studies have uncovered specific genetic alterations, transcriptomic patterns and epigenetic profiles associated with different glioma types. We have recently created a unique atlas encompassing genome-wide profiles of open chromatin, histone H3K27ac and H3Kme3 modifications, DNA methylation and transcriptomes of 33 glioma samples of different grades. Here, we intersected genome-wide atlas data with topologically associating domains (TADs) and demonstrated that the chromatin organization and epigenetic landscape of enhancers have a strong impact on genes differentially expressed in WHO low grade versus high grade gliomas. We identified TADs enriched in glioma grade-specific genes and/or epigenetic marks. We found the set of transcription factors, including REST, E2F1 and NFKB1, that are most likely to regulate gene expression in multiple TADs, containing specific glioma-related genes. Moreover, many genes associated with the cell–matrix adhesion Gene Ontology group, in particular 14 PROTOCADHERINs, were found to be regulated by long-range contacts with enhancers. Presented results demonstrate the existence of epigenetic differences associated with chromatin organization driving differential gene expression in gliomas of different malignancy.

scholarly journals Polycombs and microRNA-223 regulate human granulopoiesis by transcriptional control of target gene expression

Blood ◽  
2012 ◽  
Vol 119 (17) ◽  
pp. 4034-4046 ◽  
Author(s):  
Giuseppe Zardo ◽  
Alberto Ciolfi ◽  
Laura Vian ◽  
Linda M. Starnes ◽  
Monia Billi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Transcriptional Control ◽  
Transcriptional Level ◽  
Seed Region ◽  
Mrna Targets ◽  
Epigenetic Events ◽  
Evolutionarily Conserved ◽  
Lineage Decision ◽  
Chromatin Remodeling Complexes

Abstract Epigenetic modifications regulate developmental genes involved in stem cell identity and lineage choice. NFI-A is a posttranscriptional microRNA-223 (miR-223) target directing human hematopoietic progenitor lineage decision: NFI-A induction or silencing boosts erythropoiesis or granulopoiesis, respectively. Here we show that NFI-A promoter silencing, which allows granulopoiesis, is guaranteed by epigenetic events, including the resolution of opposing chromatin “bivalent domains,” hypermethylation, recruitment of polycomb (PcG)–RNAi complexes, and miR-223 promoter targeting activity. During granulopoiesis, miR-223 localizes inside the nucleus and targets the NFI-A promoter region containing PcGs binding sites and miR-223 complementary DNA sequences, evolutionarily conserved in mammalians. Remarkably, both the integrity of the PcGs-RNAi complex and DNA sequences matching the seed region of miR-223 are required to induce NFI-A transcriptional silencing. Moreover, ectopic miR-223 expression in human myeloid progenitors causes heterochromatic repression of NFI-A gene and channels granulopoiesis, whereas its stable knockdown produces the opposite effects. Our findings indicate that, besides the regulation of translation of mRNA targets, endogenous miRs can affect gene expression at the transcriptional level, functioning in a critical interface between chromatin remodeling complexes and the genome to direct fate lineage determination of hematopoietic progenitors.

scholarly journals Yeast DNA sequences initiating gene expression in Escherichia coli

2004 ◽  
Vol 159 (1) ◽  
pp. 19-28 ◽  
Author(s):  
Astrid Lewin ◽  
Thi Tuyen Tran ◽  
Daniela Jacob ◽  
Martin Mayer ◽  
Barbara Freytag ◽  
...  
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Dna Sequences ◽  
Expression In Escherichia Coli

scholarly journals Repression of ESR1 through Actions of Estrogen Receptor Alpha and Sin3A at the Proximal Promoter

2009 ◽  
Vol 29 (18) ◽  
pp. 4949-4958 ◽  
Author(s):  
Stephanie J. Ellison-Zelski ◽  
Natalia M. Solodin ◽  
Elaine T. Alarid
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Transcription Factor ◽  
Rna Polymerase Ii ◽  
Transcriptional Repression ◽  
Estrogen Receptor Alpha ◽  
Proximal Promoter ◽  
Receptor Alpha ◽  
Expression Of Genes ◽  
Activation Of Transcription

ABSTRACT Gene expression results from the coordinated actions of transcription factor proteins and coregulators. Estrogen receptor alpha (ERα) is a ligand-activated transcription factor that can both activate and repress the expression of genes. Activation of transcription by estrogen-bound ERα has been studied in detail, as has antagonist-induced repression, such as that which occurs by tamoxifen. How estrogen-bound ERα represses gene transcription remains unclear. In this report, we identify a new mechanism of estrogen-induced transcriptional repression by using the ERα gene, ESR1. Upon estrogen treatment, ERα is recruited to two sites on ESR1, one distal (ENH1) and the other at the proximal (A) promoter. Coactivator proteins, namely, p300 and AIB1, are found at both ERα-binding sites. However, recruitment of the Sin3A repressor, loss of RNA polymerase II, and changes in histone modifications occur only at the A promoter. Reduction of Sin3A expression by RNA interference specifically inhibits estrogen-induced repression of ESR1. Furthermore, an estrogen-responsive interaction between Sin3A and ERα is identified. These data support a model of repression wherein actions of ERα and Sin3A at the proximal promoter can overcome activating signals at distal or proximal sites and ultimately decrease gene expression.

Antibodies to chemically synthesized peptides predicted from DNA sequences as probes of gene expression

Cell ◽  
1981 ◽  
Vol 23 (2) ◽  
pp. 309-310 ◽  
Author(s):  
Richard A. Lerner ◽  
J.Gregor Sutcliffe ◽  
Thomas M. Shinnick
Keyword(s):  
Gene Expression ◽  
Dna Sequences
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