Tamar Juven-Gershon

• Ph.D.
• Full Professor at Bar Ilan University

Motivation Prediction and identification of core promoter elements and transcription factor binding sites (TFBSs) is essential for understanding the mechanism of transcription initiation and deciphering the biological activity of a specific locus. Thus, there is a need for an up-to-date tool to detect and curate core promoter elements/motifs in any...

Background The Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The five complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from g...

Transcription is initiated at the core promoter, which confers specific functions depending on the unique combination of core promoter elements. The downstream core promoter element (DPE) is found in many genes related to heart and mesodermal development. However, the function of these core promoter elements has thus far been studied primarily in i...

Neural stem cells (NSCs) in the adult and aged brain are largely quiescent, and require transcriptional reprogramming to re‐enter the cell cycle. However, the mechanisms underlying these changes and how they are altered with age remain undefined. Here, we identify the chromatin accessibility differences between primary neural stem/progenitor cells...

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 tha...

Metazoan core promoters, which direct the initiation of transcription by RNA polymerase II (Pol II), may contain short sequence motifs termed core promoter elements/motifs (e.g. the TATA box, initiator (Inr) and downstream core promoter element (DPE)), which recruit Pol II via the general transcription machinery. The DPE was discovered and extensiv...

Metazoan core promoters, which direct the initiation of transcription by RNA polymerase II (Pol II), may contain short sequence motifs termed core promoter elements/motifs ( e.g. the TATA box, initiator (Inr) and downstream core promoter element (DPE)), which recruit Pol II via the general transcription machinery. The DPE was discovered and extensi...

Background: The generation of point mutations is a major tool for evaluating the roles of specific nucleotides or amino acids within the regulatory or functional landscape. However, examination of these mutations in vivo requires the generation of animals carrying only the relevant point mutations at the endogenous genomic loci, which is technical...

Transcription factors encoded by Homeobox (HOX) genes play numerous key functions during early embryonic development and differentiation. Multiple reports have shown that mis-regulation of HOX gene expression plays key roles in the development of cancers. Their expression levels in cancers tend to differ based on tissue and tumor type. Here, we per...

TRF2 (TATA-box-binding protein-related factor 2) is an evolutionarily conserved general transcription factor that is essential for embryonic development of Drosophila melanogaster, C. elegans , zebrafish and Xenopus . Nevertheless, the cellular processes that are regulated by TRF2 are largely underexplored. Here, using Drosophila Schneider cells as...

Adult neural stem cells are largely quiescent, and require transcriptional reprogramming to reenter the cell cycle and undergo neurogenesis. However, the precise mechanisms that underlie the rapid transcriptional overhaul during NSC activation remain undefined. Here, we identify the genome-wide chromatin accessibility differences between primary ne...

Integrative analysis of high‐throughput reporter assays, machine learning, and profiles of epigenomic chromatin state in a broad array of cells and tissues has the potential to significantly improve our understanding of non‐coding regulatory element function and its contribution to human disease. Here we report results from the CAGI 5 regulation sa...

The regulation of transcription initiation is critical for developmental and cellular processes. RNA polymerase II (Pol II) is recruited by the basal transcription machinery to the core promoter where Pol II initiates transcription. The core promoter encompasses the region from -40 to +40 bp relative to the +1 transcription start site (TSS). Core p...

The core promoter is the DNA sequence that recruits the basal transcription machinery and directs accurate initiation of transcription. It is an active contributor to gene expression that can be rationally designed to manipulate the levels of expression. Core promoter function can be analyzed using different experimental approaches. Here, we descri...

CueR (Cu export regulator) is a metalloregulator protein that “senses” Cu(I) ions with very high affinity, thereby stimulating DNA binding and the transcription activation of two other metalloregulator proteins. The crystal structures of CueR when unbound or bound to DNA and a metal ion are very similar to each other, and the role of CueR and Cu(I)...

Transcription factors (TFs) alter gene expression in response to changes in the environment through sequence-specific interactions with the DNA. These interactions are best portrayed as a landscape of TF binding affinities. Current methods to study sequence-specific binding preferences suffer from limited dynamic range, sequence bias, lack of speci...

The core promoter, which is generally defined as the region to which RNA Polymerase II is recruited to initiate transcription, plays a pivotal role in the regulation of gene expression. The core promoter consists of different combinations of several short DNA sequences, termed core promoter elements or motifs, which confer specific functional prope...

Schematic illustration of the constructed EGFP expression plasmids driven by the various core promoters linked to the CMV enhancer. The EGFP gene was cloned into the HindIII and XbaI sites of the commercial pRc/CMV plasmid (Life Technologies). The CMV enhancer was amplified using PCR and the promoters of the natural CMV, SCP2 and SCP3 were cloned i...

Flow cytometric analysis of long-term average fluorescence intensity and average number of fluorescent HeLa S3 and SH-SY5Y cells. HeLa S3 and SH-SY5Y cells were transiently transfected with pRc/CMV, natural CMV, SCP2 or SCP3 vector expressing EGFP. The cells were collected 4–8 days post-transfection (P.T.) for flow cytometric analysis. (A) Flow cyt...

Flow cytometric analysis of short and long -term average fluorescence intensity and average number of fluorescent HOP-92 cells. HOP-92 cells were transiently transfected with pRc/CMV, natural CMV, SCP2 or SCP3 vector expressing EGFP. The cells were collected 1–4 and 4–8 days post-transfection (P.T.) for flow cytometric analysis. (A) Flow cytometric...

Assessment of primers’ quality by qPCR total DNA purified from transiently trasnfected HeLa S3 and SH-SY5Y cells. HeLa S3 and SH-SY5Y cells were transiently transfected with the SCP3 vector expressing EGFP, and harvested 4 days post-transfection (P.T.). Total DNA was purified from cells and subjected to qPCR analysis with primers for the GAPDH, EGF...

Live cell imaging of SH-SY5Y cells expressing EGFP that is driven by pRc/CMV-based constructs for over 30 days. SH-SY5Y cells were transiently transfected with either pRc/CMV, natural CMV, SCP2 or SCP3 vector expressing EGFP. The cells were imaged over a 31 days period post-transfection (P.T.). Each circle displays the whole well image constructed...

Flow cytometric analysis of short-term average fluorescence intensity and average number of fluorescent HeLa S3 and SH-SY5Y cells. HeLa S3 and SH-SY5Y cells were transiently transfected with pRc/CMV, natural CMV, SCP2 or SCP3 vector expressing EGFP. The cells were collected 1–4 days post-transfection (P.T.) for flow cytometric analysis. (A) Flow cy...

Supporting Information—Methods. (PDF)

Real-Time quantitative PCR of purified transiently transfected plasmid DNA in HeLa S3 and SH-SY5Y cells. HeLa S3 and SH-SY5Y cells were transiently transfected with pRc/CMV, natural CMV, SCP2 or SCP3 vector expressing EGFP, and harvested on days 2, 4, 6, 8 and 14 post-transfection (P.T.). Plasmid DNA was purified from cells and subjected to qPCR an...

Core promoter elements play a pivotal role in the transcriptional output, yet they are often detected manually within sequences of interest. Here, we present 2 contributions to the detection and curation of core promoter elements within given sequences. First, the Elements Navigation Tool (ElemeNT) is a user-friendly web-based, interactive tool for...

Regulation of RNA polymerase II transcription is critical for the proper development, differentiation and growth of an organism. The RNA polymerase II core promoter is the ultimate target of a multitude of transcription factors that control transcription initiation. Core promoters encompass the RNA start site and consist of functional elements such...

Abstract Transcriptional regulation is pivotal for development and differentiation of organisms. Transcription of eukaryotic protein-coding genes by RNA polymerase II (Pol II) initiates at the core promoter. Core promoters, which encompass the transcription start site, may contain functional core promoter elements, such as the TATA box, initiator,...

The unfolded protein response (UPR) allows cells to adjust the capacity of the endoplasmic reticulum (ER) to the load of ER-associated tasks. We show that activation of the Caenorhabditis elegans transcription factor DAF-16 and its human homolog FOXO3 restore secretory protein metabolism when the UPR is dysfunctional. We show that DAF-16 establishe...

Transcription of protein-coding genes is highly dependent on the RNA polymerase II core promoter. Core promoters, generally defined as the regions that direct transcription initiation, consist of functional core promoter motifs (such as the TATA-box, initiator [Inr], and downstream core promoter element [DPE]) that confer specific properties to the...

Developmental processes are highly dependent on transcriptional regulation by RNA polymerase II, which initiates transcription at the core promoter. The dorsal-ventral gene regulatory network (GRN) includes multiple genes that are activated by different nuclear concentrations of the Dorsal transcription factor along the dorsal-ventral axis. Downstr...

Developmental processes are highly dependent on transcriptional regulation by RNA polymerase II. The RNA polymerase II core promoter is the ultimate target of a multitude of transcription factors that control transcription initiation. Core promoters consist of core promoter motifs, e.g. the initiator, TATA box, and the downstream core promoter elem...

A mechanistic description of metazoan transcription is essential for understanding the molecular processes that govern cellular decisions. To provide structural insights into the DNA recognition step of transcription initiation, we used single-particle electron microscopy (EM) to visualize human TFIID with promoter DNA. This analysis revealed that...

The RNA polymerase II core promoter is a structurally and functionally diverse transcriptional regulatory element. There are two main strategies for transcription initiation - focused and dispersed initiation. In focused initiation, transcription starts from a single nucleotide or within a cluster of several nucleotides, whereas in dispersed initia...

The regulation of gene transcription is critical for the proper development and growth of an organism. The transcription of protein-coding genes initiates at the RNA polymerase II core promoter, which is a diverse module that can be controlled by many different elements such as the TATA box and downstream core promoter element (DPE). To understand...

The RNA polymerase II core promoter is a structurally and functionally diverse transcriptional module. RNAi depletion and overexpression experiments revealed a genetic circuit that controls the balance of transcription from two core promoter motifs, the TATA box and the downstream core promoter element (DPE). In this circuit, TBP activates TATA-dep...

The RNA polymerase II core promoter is generally defined to be the sequence that directs the initiation of transcription. This simple definition belies a diverse and complex transcriptional module. There are two major types of core promoters - focused and dispersed. Focused promoters contain either a single transcription start site or a distinct cl...

Transcription is a critical component in the expression of genes. Here we describe the design and analysis of a potent core promoter, termed super core promoter 1 (SCP1), which directs high amounts of transcription by RNA polymerase II in metazoans. SCP1 contains four core promoter motifs-the TATA box, initiator (Inr), motif ten element (MTE) and d...

The Drosophila Seven in absentia (Sina) gene product originally was described as a protein that controls cell fate decisions during eye development. Its mammalian homolog, Siah-1, recently was found to be involved in p53-dependent and -independent pathways of apoptosis and G1 arrest. We report that Siah-1 interacts directly with and promotes the de...

In response to environmental stress, the p53 phosphoprotein is stabilized and activated to inhibit cell growth. p53 stability and activity are negatively regulated by the murine double minute (Mdm2) oncoprotein in an autoregulatory feedback loop. The inhibitory effect of Mdm2 on p53 has to be tightly regulated for proper p53 activity. Phosphorylati...

The p53 tumor suppressor gene is mutated in over 50% of human cancers, resulting in inactivation of the wild-type (wt) p53 protein. The most notable biochemical feature of p53 is its ability to act as a sequence-specific transcriptional activator. Through use of the suppression subtractive hybridization differential screening technique, we identifi...

The Mdm2 oncoprotein is a well-known inhibitor of the p53 tumor suppressor, but it may also possess p53-independent activities. In search of such p53-independent activities, the yeast two-hybrid screen was employed to identify Mdm2-binding proteins. We report that in vitro and in transfected cells, Mdm2 can associate with Numb, a protein involved i...

The mdm2 proto-oncogene product binds to the p53 tumor suppressor protein and inhibits its ability to trans-activate target genes. One such target gene is mdm2 itself, which is therefore considered a component of a p53 negative feedback loop. Two tandem p53-binding motifs residing within the first intron of the murine mdm2 gene confer upon it p53-m...

Sera of normal controls and of patients with neurological diseases contain antineurofilament antibodies. Recent studies suggest that biochemically and immunologically distinct subclasses of neurofilaments occur in different types of neurons. Alzheimer's disease (AD), the major cause of dementia, is associated with a marked degeneration of brain cho...

Excerpt The p53 protein is the product of a tumor suppressor gene which is subject to an extremely high frequency of structural alterations in human cancer (for review, see Hollstein et al. 1991; Levine et al. 1991; Oren 1992; Donehower and Bradley 1993; Harris and Hollstein 1993; Berns 1994). The main selective advantage of such alterations is pro...

We have recently characterized a 95 kDa protein, p95, which exhibits enhanced binding to temperature-sensitive p53 (ts-p53) when cells are shifted down to 32.5 degrees C, a temperature at which ts-p53 possesses wild-type (wt)-like activities. In the present study we show that p95 is a product of the mdm2 putative proto-oncogene. The enhanced comple...