scholarly journals Specialized Rap1p/Gcr1p Transcriptional Activation Through Gcr1p DNA Contacts Requires Gcr2p, as Does Hyperphosphorylation of Gcr1p

Genetics ◽  
1997 ◽  
Vol 147 (2) ◽  
pp. 493-505 ◽  
Author(s):  
Xiao Zeng ◽  
Stephen J Deminoff ◽  
George M Santangelo

The multifunctional regulatory factor Rap1p of Saccharomyces cerevisiae accomplishes one of its tasks, transcriptional activation, by complexing with Gcr1p. An unusual feature of this heteromeric complex is its apparent capacity to contact simultaneously two adjacent DNA elements (UASRPG and the CT box, bound specifically by Rap1p and Gcr1p, respectively). The complex can activate transcription through isolated UASRPG but not CT elements. In promoters that contain both DNA signals its activity is enhanced, provided the helical spacing between the two elements is appropriate; this suggests that at least transient DNA loop formation is involved. We show here that this CT box-dependent augmentation of Rap1p/Gcr1p activation requires the presence of a third protein Gcr2p; the Gcr2– growth defect appears to result from a genome-wide loss of the CT box effect. Interestingly, a hyperphosphorylated form of Gcr1p disappears in Δgcr2 cells but reappears if they harbor a doubly point-mutated GCR1 allele that bypasses the Gcr2– growth defect. Gcr2p therefore appears to induce a conformation change in Gcr1p and/or stimulate its hyperphosphorylation; one or both of these effects can be mimicked in the absence of GCR2 by mutation of GCR1. This improved view of Rap1p/Gcr1p/Gcr2p function reveals a new aspect of eukaryotic gene regulation: modification of an upstream activator, accompanied by at least transient DNA loop formation, mediates its improved capacity to activate transcription.

2019 ◽  
Author(s):  
Zeineb Achour ◽  
Johann Joets ◽  
Martine Leguilloux ◽  
Hélène Sellier ◽  
Jean-Philippe Pichon ◽  
...  

ABSTRACTCharacterizing the molecular processes developed by plants to respond to environmental cues is a major task to better understand local adaptation. DNA methylation is a chromatin mark involved in the transcriptional silencing of transposable elements (TEs) and gene expression regulation. While the molecular bases of DNA methylation regulation are now well described, involvement of DNA methylation in plant response to environmental cues remains poorly characterized. Here, using the TE-rich maize genome and analyzing methylome response to prolonged cold at the chromosome and feature scales, we investigate how genomic architecture affects methylome response to stress in a cold-sensitive genotype. Interestingly, we show that cold stress induces a genome-wide methylation increase through the hypermethylation of TE sequences and centromeres. Our work highlights a cytosine context-specific response of TE methylation that depends on TE types, chromosomal location and proximity to genes. The patterns observed can be explained by the parallel transcriptional activation of multiple DNA methylation pathways that methylate TEs in the various chromatin locations where they reside. Our results open new insights into the possible role of genome-wide DNA methylation in phenotypic response to stress.


Author(s):  
Soichirou Satoh ◽  
Takayuki Hata ◽  
Naoto Takada ◽  
Makoto Tachikawa ◽  
Mitsuhiro Matsuo ◽  
...  

ABSTRACTHorizontal gene transfer can occur between phylogenetically distant organisms, such as prokaryotes and eukaryotes. In these cases, how do the translocated genes acquire transcriptional competency in the alien genome environment? According to the conventional view, specific loci of the eukaryotic genome are thought to provide transcriptional competency to the incoming coding sequences. To examine this possibility, we randomly introduced the promoterless luciferase (LUC)-coding sequences into the genome of Arabidopsis thaliana cultured cells and performed a genome-wide “transgene location vs. expression” scan. We found that one-third of the 4,504 mapped LUC genes were transcribed. However, only 10% of them were explained by conventional transcriptional fusions with the annotated genes, and the remainder of the genes exhibited novel transcription that occurred independently of the chromatin configuration or transcriptional activity inherent to the given chromosomal locus; rather, their transcriptional activation occurred stochastically at about 30% of each insertion event, but independent of the integration sites. We termed this activation phenomenon as an integration-dependent stochastic transcriptional activation, a new type of response of the plant genome to incoming coding sequences. We discuss the possible roles of this phenomenon in the evolution of eukaryotic genomes.


2016 ◽  
Author(s):  
Maria Tsochatzidou ◽  
Maria Malliarou ◽  
Nikolas Papanikolaou ◽  
Joaquim Roca ◽  
Christoforos Nikolaou

AbstractThe eukaryotic genome evolves under the dual constraint of maintaining co-ordinated gene transcription and performing effective DNA replication and cell division, the coupling of which brings about inevitable DNA topological tension. DNA supercoiling is resolved and, in some cases, even harnessed by the genome through the function of DNA topoisomerases, as has been shown in the concurrent transcriptional activation and suppression of genes upon transient deactivation of topoisomerase II (topoII). By analyzing a genome wide run-on experiment upon thermal inactivation of topoII in S.cerevisiae. we were able to define 116 gene clusters of consistent response (either positive or negative) to topological stress. A comprehensive analysis of these topologically co-regulated gene clusters revealed pronounced preferences regarding their functional, regulatory and structural attributes. Genes that negatively respond to topological stress, are positioned in gene-dense pericentromeric regions, are more conserved and associated to essential functions, while up-regulated gene clusters are preferentially located in the gene-sparse nuclear periphery, associated with secondary functions and under complex regulatory control. We propose that evolves with a core of essential genes occupying a compact genomic “old town”, whereas more recently acquired, condition-specific genes tend to be located in a more spacious “suburban” genomic periphery.


2021 ◽  
Vol 22 (24) ◽  
pp. 13568
Author(s):  
Zhengfu Yang ◽  
Hongmiao Jin ◽  
Junhao Chen ◽  
Caiyun Li ◽  
Jiani Wang ◽  
...  

The AP2 transcriptional factors (TFs) belong to the APETALA2/ ethylene-responsive factor (AP2/ERF) superfamily and regulate various biological processes of plant growth and development, as well as response to biotic and abiotic stresses. However, genome-wide research on the AP2 subfamily TFs in the pecan (Carya illinoinensis) is rarely reported. In this paper, we identify 30 AP2 subfamily genes from pecans through a genome-wide search, and they were unevenly distributed on the pecan chromosomes. Then, a phylogenetic tree, gene structure and conserved motifs were further analyzed. The 30 AP2 genes were divided into euAP2, euANT and basalANT three clades. Moreover, the cis-acting elements analysis showed many light responsive elements, plant hormone-responsive elements and abiotic stress responsive elements are found in CiAP2 promoters. Furthermore, a qPCR analysis showed that genes clustered together usually shared similar expression patterns in euAP2 and basalANT clades, while the expression pattern in the euANT clade varied greatly. In developing pecan fruits, CiAP2-5, CiANT1 and CiANT2 shared similar expression patterns, and their expression levels decreased with fruit development. CiANT5 displayed the highest expression levels in developing fruits. The subcellular localization and transcriptional activation activity assay demonstrated that CiANT5 is located in the nucleus and functions as a transcription factor with transcriptional activation activity. These results help to comprehensively understand the pecan AP2 subfamily TFs and lay the foundation for further functional research on pecan AP2 family genes.


Blood ◽  
2012 ◽  
Vol 119 (2) ◽  
pp. 388-398 ◽  
Author(s):  
Yongsheng Huang ◽  
Kajal Sitwala ◽  
Joel Bronstein ◽  
Daniel Sanders ◽  
Monisha Dandekar ◽  
...  

The clustered homeobox proteins play crucial roles in development, hematopoiesis, and leukemia, yet the targets they regulate and their mechanisms of action are poorly understood. Here, we identified the binding sites for Hoxa9 and the Hox cofactor Meis1 on a genome-wide level and profiled their associated epigenetic modifications and transcriptional targets. Hoxa9 and the Hox cofactor Meis1 cobind at hundreds of highly evolutionarily conserved sites, most of which are distant from transcription start sites. These sites show high levels of histone H3K4 monomethylation and CBP/P300 binding characteristic of enhancers. Furthermore, a subset of these sites shows enhancer activity in transient transfection assays. Many Hoxa9 and Meis1 binding sites are also bound by PU.1 and other lineage-restricted transcription factors previously implicated in establishment of myeloid enhancers. Conditional Hoxa9 activation is associated with CBP/P300 recruitment, histone acetylation, and transcriptional activation of a network of proto-oncogenes, including Erg, Flt3, Lmo2, Myb, and Sox4. Collectively, this work suggests that Hoxa9 regulates transcription by interacting with enhancers of genes important for hematopoiesis and leukemia.


2021 ◽  
Vol 7 (20) ◽  
pp. eabf2229
Author(s):  
Bastian Stielow ◽  
Yuqiao Zhou ◽  
Yinghua Cao ◽  
Clara Simon ◽  
Hans-Martin Pogoda ◽  
...  

CpG islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here, we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 has an atypical winged-helix domain that directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove. The SAM domain interacts with L3MBTL3, but it can also homopolymerize into a closed pentameric ring. At a genome-wide level, SAMD1 localizes to H3K4me3-decorated CGIs, where it acts as a repressor. SAMD1 tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs, thereby providing a mechanism for SAMD1-mediated transcriptional repression. The absence of SAMD1 impairs ES cell differentiation processes, leading to misregulation of key biological pathways. Together, our work establishes SAMD1 as a newly identified chromatin regulator acting at unmethylated CGIs.


2016 ◽  
Vol 1 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Parul Mehra ◽  
Tatiana Gerasimova ◽  
Arindam Basu ◽  
Vibha Jha ◽  
Anupam Banerjee ◽  
...  

Key Points Transcription factor YY1 regulates the IgH Eμ-3′RR long-distance DNA loop without the YY1 transcriptional activation domain. YY1 constructs that rescue the Eμ-3′RR DNA loop also restore CSR strongly arguing for the necessity of this long-distance DNA loop for CSR.


Blood ◽  
2019 ◽  
Vol 133 (7) ◽  
pp. 724-729 ◽  
Author(s):  
Maoxiang Qian ◽  
Heng Xu ◽  
Virginia Perez-Andreu ◽  
Kathryn G. Roberts ◽  
Hui Zhang ◽  
...  

Abstract Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Characterized by high levels of Native American ancestry, Hispanics are disproportionally affected by this cancer with high incidence and inferior survival. However, the genetic basis for this disparity remains poorly understood because of a paucity of genome-wide investigation of ALL in Hispanics. Performing a genome-wide association study (GWAS) in 940 Hispanic children with ALL and 681 ancestry-matched non-ALL controls, we identified a novel susceptibility locus in the ERG gene (rs2836365; P = 3.76 × 10−8; odds ratio [OR] = 1.56), with independent validation (P = .01; OR = 1.43). Imputation analyses pointed to a single causal variant driving the association signal at this locus overlapping with putative regulatory DNA elements. The effect size of the ERG risk variant rose with increasing Native American genetic ancestry. The ERG risk genotype was underrepresented in ALL with the ETV6-RUNX1 fusion (P < .0005) but enriched in the TCF3-PBX1 subtype (P < .05). Interestingly, ALL cases with germline ERG risk alleles were significantly less likely to have somatic ERG deletion (P < .05). Our results provide novel insights into genetic predisposition to ALL and its contribution to racial disparity in this cancer.


2014 ◽  
Vol 35 (1) ◽  
pp. 331-342 ◽  
Author(s):  
Emily Paul ◽  
Z. Iris Zhu ◽  
David Landsman ◽  
Randall H. Morse

Mediator is a large, multisubunit complex that is required for essentially all mRNA transcription in eukaryotes. In spite of the importance of Mediator, the range of its targets and how it is recruited to these is not well understood. Previous work showed that inSaccharomyces cerevisiae, Mediator contributes to transcriptional activation by two distinct mechanisms, one depending on the tail module triad and favoring SAGA-regulated genes, and the second occurring independently of the tail module and favoring TFIID-regulated genes. Here, we use chromatin immunoprecipitation sequencing (ChIP-seq) to show that dependence on tail module subunits for Mediator recruitment and polymerase II (Pol II) association occurs preferentially at SAGA-regulated over TFIID-regulated genes on a genome-wide scale. We also show that recruitment of tail module subunits to active gene promoters continues genome-wide when Mediator integrity is compromised inmed17temperature-sensitive (ts) yeast, demonstrating the modular nature of the Mediator complexin vivo. In addition, our data indicate that promoters exhibiting strong and stable occupancy by Mediator have a wide range of activity and are enriched for targets of the Tup1-Cyc8 repressor complex. We also identify a number of strong Mediator occupancy peaks that overlap dubious open reading frames (ORFs) and are likely to include previously unrecognized upstream activator sequences.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243791
Author(s):  
Caitlin Mills ◽  
Anushya Muruganujan ◽  
Dustin Ebert ◽  
Crystal N. Marconett ◽  
Juan Pablo Lewinger ◽  
...  

Enhancers are powerful and versatile agents of cell-type specific gene regulation, which are thought to play key roles in human disease. Enhancers are short DNA elements that function primarily as clusters of transcription factor binding sites that are spatially coordinated to regulate expression of one or more specific target genes. These regulatory connections between enhancers and target genes can therefore be characterized as enhancer-gene links that can affect development, disease, and homeostatic cellular processes. Despite their implication in disease and the establishment of cell identity during development, most enhancer-gene links remain unknown. Here we introduce a new, publicly accessible database of predicted enhancer-gene links, PEREGRINE. The PEREGRINE human enhancer-gene links interactive web interface incorporates publicly available experimental data from ChIA-PET, eQTL, and Hi-C assays across 78 cell and tissue types to link 449,627 enhancers to 17,643 protein-coding genes. These enhancer-gene links are made available through the new Enhancer module of the PANTHER database and website where the user may easily access the evidence for each enhancer-gene link, as well as query by target gene and enhancer location.


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