Research - Institute of Biochemistry - Eukaryotic Molecular Biology Unit - Laboratory of Cell Cycle - Intracellular Protein Degradation / Transcription Regulation

Imre BOROS
Principal Investigator

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Ecaterina Edith VAMOS Staff Scientist
Gyuláné ÖKRÖS Technician

EUKARYOTIC TRANSCRIPTION REGULATION

Transcription of eukaryotic genes is a multistep process that involves the interaction of a large number of functionally different protein factors and requires the ordered assembly of giant multiprotein complexes in gene regulatory regions. Understanding the role of functionally distinct classes of transcription regulatory proteins is a key to uncovering cellular processes and deciphering why and how those are de-regulated in diseases.


In joint laboratories located at the BRC and at the Biochemistry and Molecular Biology Department of Szeged University we use biochemical and genetic approaches to tackle problems related to transcription regulation. Ongoing research projects of the laboratory target different participants of the transcription process. Some of the factors studied play a direct role in RNA synthesis (Pol II CTD, RPB4), others regulate the activity of the Pol II complex (FCP1, p53), and further ones are modifiers of chromatin structure (SAGA and ATAC complexes).

Recent results of the group on the functional analysis of genes encoding transcriptional coactivators (Ada2a, Ada2b, Ada3) have lead to the discovery of two Drosophila histone acetyltransferase (HAT) complexes: SAGA and ATAC, sharing a common acetyltransferase subunit: GCN5. By detailed analysis of the effects of mutations in shared and complex-specific subunits of SAGA and ATAC we have shown that by acetylating histone H3 and H4 lysine residues these complexes regulate different sets of genes and various chromatin-associated processes. The demonstration of the functional interconnection of histone acetylation, phosphorylation and methylation is a fine in vivo example for a molecular mechanism of complex histone modification pattern formation which contributes to epigenetic mechanisms.




Selected publications

Ciurciu, A., Komonyi, O., Pankotai, T. and Boros, I. (2006). The Drosophila histone acetyltranferase gcn5 and transcriptional adaptor ada2a are involved in nucleosomal histone h4 acetylation. Mol. Cell. Biol. 26(24): 9413-9423.

Bodai, L., Pardi, N., Ujfaludi, Z., Bereczki, O., Komonyi, O., Bálint, É. and Boros, I.M. (2007). Daxx-like protein of Drosophila interacts with Dmp53 and affects longevity and Ark mRNA level. J. Biol. Chem. 282(50): 36386-36393.

Carré, C., Ciurciu, A., Komonyi, O., Jacquier, C., Fagegaltier, D., Pidoux, Tricoire, H., Tora, L., Boros, I. and Antoniewski, C. (2008). The NURF remodeling complex and the ATAC histone acetylase complex cooperate in the maintenance of high order chromosome structure. EMBO Rep. 9: 187-92.

B. Grau, B., Popescu, C., Torroja, L., Ortuño-Sahagún, D., Boros, I. and Ferrús, A. (2008). The transcriptional adaptor Ada3 of Drosophila is required for histone modification, position effect variegation and transcription. Mol. Cell. Biol. 28(1): 376-85.

Bereczki, O., Ujfaludi, Z., Pardi, N., Nagy, Z., Tora, L., Boros, I.M. and Bálint, É. (2008). TATA binding protein associated factor 3 (TAF3) interacts with p53 and inhibits its function. BMC Molecular Biology 9: 57.

Ciurciu, A., Komonyi, O. and Boros, I.M. (2008). Loss of ATAC-specific histone H4 lysine 12 acetylation reduces JIL-1 binding to chromatin and phosphorylation of histoneH3 at serine 10. J. Cell Science 121: 3366-3372.

Ciurciu, A., Tombácz, I., Popescu, C. and Boros, I. (2009). GAL4 induces transcriptionally active puff in the absence of JIL-1, dSAGA and ATAC specific chromatin modifications in the Drosophila melanogaster polytene chromosome. Chromosoma, in press.

Schauer, T., Tombácz, I., Ciurciu, A., Komonyi, O. and Boros, I. (2009). Misregulated RNA Pol II CTD phosphorylation results in apoptosis. Cell. Mol. Life. Sci. 66(5): 909-918.

Komonyi, O., Schauer, T., Pápai, G., Deák, P. and Boros, I.M. (2009). A product of the bicistronic CG31241 Drosophila melanogaster gene interplays with ATR but acts independently of ATM in telomere protection. J. Cell Science 122: 769-774.