Prof. Rivka Dikstein

Prof. Rivka Dikstein
Phone: +972-8-934-2117; Fax: +972-8-934-4118
Email: rivka.dikstein@weizmann.ac.il


Regulation of Gene Expression:
from Transcription Initiation and Elongation to mRNA Translation

Expression of protein encoding and non-coding genes is an intricate and highly regulated process that produces a remarkable diversity of gene expression patterns. Elucidation of the mechanisms that generate such diversity is an important challenge and the primary goal of the research in our lab.


We are investigating the mechanism underlying transcriptional control of coding and non-coding RNAs, focusing on the initiation and elongation stages. In addition we study a unique form of translation initiation that is linked to transcription.


Basal Transcription

  1. The mammalian core promoter

    The core promoter of eukaryotic coding and non-coding genes is composed of DNA elements surrounding the transcription start site. These elements serve as the docking site of the basal transcription machinery and have an important role in determining the position and directing the rate of transcription initiation. For many years the core promoter was thought to be a universal element common to most genes. However sequence analysis has revealed unexpected diversity among core promoters. The best-known element, the TATA box is found in only ~20% of human promoters and many promoters do not contain any known core promoter elements.

    To investigate the mammalian core promoter we are combining bioinformatics, molecular and biochemical tools. Our findings of the past few years revealed important new features of the mammalian core promoter and provide insights into its evolution. We found unexpected links between core promoter elements (initiation) and other features that influence gene expression including transcription elongation4, protein translation8, 13 gene size and gene function7.

  2. TFIID

    Among the general transcription factors TFIID is the major core promoter-binding factor. TFIID is comprised of the TATA-binding protein (TBP) and 14 TBP-associated factors (TAFs). TAFs control transcription at multiple levels and possess gene-specific as well as general functions. Although our understanding of TFIID is continuously expanding, to date our knowledge on the specific function of individual TAFs is still very limited. We are investigating the function of a subset of histone-fold containing TAFs by characterizing their biochemical properties, their core promoter functions, their relations with other transcription regulators and their physiological functions3, 9, 10, 14, 18.

Links between transcription and translation: TISU genes

One of the interesting proximal element that we have identified is TISU, an element that is located downstream relative to the TSS between +5 to +30, specifically in TATA-less promoters2. Remarkably, in addition to its contribution to promoter strength it also serves as a strong translation initiator that is optimized to function in mRNAs with very short 5'UTR2, 3. This element directs a novel mode of translation initiation that is cap dependent but scanning independent8, 13. Our goals are to elucidate the mechanisms and the biological significance of transcription and translation control through TISU.

Regulated Transcription

  1. NF-kB

    An activated transcription regulatory pathway that we are studying involves the transcription factor NF-kB. NF-kB controls the expression of genes involved in immune responses, viral infections, cytokine signaling and stress. While the NF-kB signaling pathways have been studied in great detail, much less is known about the nuclear events that lead to activation of genes by NF-kB.

    Our goal is to decipher the molecular means by which NF-kB activates the transcription of its native target genes. We have previously determined how, in principle, NF-kB-regulated genes are rapidly activated in response to extra-cellular signals1. Subsequently we found that these genes are differentially controlled at the elongation step by positive and negative elongation factors2,4. Most recently we have discovered a novel mode of co-transcriptional mRNA processing that operates without the phosphorylation of Pol II CTD by P-TEFb17, 21.

  2. MicroRNA transcription

    MicroRNAs are non-coding small RNAs that silence the expression of target genes. Beside the fact that microRNAs are transcribed by Pol II very little is known about the transcription regulation of the microRNA genes. Our goal is to determine the properties of microRNA transcription by combining bioinformatics and molecular tools. Through the analysis of miR-22 gene11 we have recently identified a novel core promoter element that is present in ~11% of genes20. Moreover we found that core promoter type can substantially impact the efficiency of nuclear processing of microRNA genes19.

Selected Publications

  1. Ainbinder, E., Revach, M. Wolstein, O. Moshonov, S. Diamant, N. Dikstein, R. (2002). Mechanism of rapid transcriptional induction of tumor necrosis factor alpha-responsive genes by NF-kB. Mol. Cell. Biol. 22 (2002): 6354-6362.
  2. Ainbinder, E., Amir-Zilberstein, L., Yamaguchi, Y., Handa, H. and Dikstein R. (2004). Elongation inhibition by DSIF is regulated by the A20 promoter via a novel negative element and NF-kB. Mol. Cell. Biol. 24:2444-2454.
  3. Shao, H., Revach, M., Moshonov, S., Tzuman Y., Gazit, K., Albeck, S., Unger. T., Dikstein R. (2005). Core promoter binding by histone fold-like TAF complexes. Mol. Cell. Biol. 25:206-219.
  4. Amir-Zilberstein, L., Ainbinder, E., Toube, L., Yamaguchi, Y. Hiroshi Handa and Dikstein, R. (2007). Differential regulation of NF-kB by elongation factors is determined by core promoter type. Mol. Cell. Biol. 27:5246-5259.
  5. Lantner, F., Starlets, D., Gore, Y., Flaishon, L., Yamit-Hezi, A., Dikstein R., Leng, L., Bucala, R., Machluf, Y., Oren, M., Shachar I. (2007). CD74 induces TAp63 expression leading to B cell survival. Blood 110:4303-4311.
  6. Amir-Zilberstein and Dikstein R. (2008). Interplay between E-box and NF-kB in regulation of A20 gene by DSIF. J. Biol. Chem. 283:1317-1323.
  7. Moshonov, S., Elfakess, R., Golan-Mashiach, M., Sinvani, H. and Dikstein, R. (2008). Links between core promoter and basic gene features influence gene expression. BMC Genomics 9:92-96.
  8. Elfakess R. and Dikstein R. (2008). A Translation Initiation Element Specific to mRNAs with Very Short 5'UTR that also Regulates Transcription. PLoS ONE. 3(8):e3094.
  9. Yarden G., Elfakess R. and Dikstein R. (2009). Characterization of sINR, a strict version of the Initiator core promoter element. Nucleic Acids Res. 37:4234-4246.
  10. Gazit, K. Moshonov, S., Elfakess, R., Sharon, M., Mengus, G., Davidson, I. and Dikstein R. (2009). TAF4/4b-TAF12 displays a unique mode of DNA binding and is required for core promoter function of a subset of genes. J. Biol. Chem. 284:26286-26296.
  11. Bar, N. and Dikstein, R. (2009). miR-22 forms a regulatory loop in PTEN/AKT pathway and modulates signaling kinetics. PLoS One 5(5):e10859.
  12. Kalogeropoulou M., Voulgari A., Kostourou V., Sandaltzopoulos R., Dikstein R., Davidson I., Tora L., Pintzas A. (2010). TAF4b and Jun/activating protein-1 collaborate to regulate the expression of integrin alpha6 and cancer cell migration properties. Mol Cancer Res. 8(4):554-68.
  13. Elfakess, R., Sinvani, H., Haimov, O., Svitkin, Y., Sonenberg, N. and Dikstein, R. (2011). Unique translation initiation of mRNAs containing TISU. Nucleic Acids Res. 39:7598-7609.
  14. Dikstein, R. (2011). The unexpected traits associated with core promoter elements. Transcription 2:207-212.
  15. Dikstein, R. (2012). Transcription and translation in a package deal: the TISU paradigm. Gene, 491:1-4.
  16. Golan-Mashiach, M., Grunspan, M., Emmanuel R.,, Gibbs-Bar, L., Dikstein, R*. and Shapiro, E* (2012). Identification of CCTC-binding factor (CTCF) as a Master Regulator of the Clustered Protocadherin Genes. Nucleic Acids Res, 40:3378-3391.
  17. Diamant, G., Amir, L. Yamaguchi, Y., Handa, H. and Dikstein R. (2012). DSIF Restricts NF-kB Signaling by Coordinating Elongation with mRNA Processing of Negative Feedback Genes. Cell Reports, 4:722-731.
  18. Bahat, A., Kedmi, R., Gazit, K., Richardo-Lax, I., Ainbinder, E. and Dikstein, R. (2013) TAF4b and TAF4 Differentially Regulate Mouse Embryonic Stem Cells Maintenance and Proliferation. In press.
  19. Marbach-Bar, N., Ben-Noon, A., Tamarkin-Ben-Harush A., Avnit-Sagi, T., Walker, M. D. and Dikstein, R. (2013). Disparity between microRNA levels and promoter strength is associated with rates of initiation and Pol II pausing at micorRNA sites. Submitted.
  20. Marbach-Bar, N., Elfakess, R., Golan-Mashiach, M., Ashkenazi, S., Chiang C-M., and Dikstein, R. DTIE, a novel downstream core promoter element directing strict transcription start sites in a TATA-less cancer-associated genes. Submitted.
  21. Diamant, G. and Dikstein R. Transcriptional Control By NF-kB: Elongation In Focus. Submitted.