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Combinatorial control of transcription is a well established phenomenon in the cell. Multiple transcription factors often bind to the same transcriptional control region of a gene and interact with each other to control the expression of the gene. It is thus necessary to consider the joint conservation of sequence pairs in order to identify combinations of binding sites to which the transcription factors bind. Conventional motif finding algorithms fail to address this issue. We propose a novel biclustering algorithm based on random sampling to identify candidate binding site combinations. We establish bounds on the various parameters to the algorithm and study the conditions under which the algorithm is guaranteed to identify candidate binding sites. We analyzed a yeast cell cycle gene expression data set using our algorithm and recovered certain novel combinations of binding sites, besides those already reported in the literature. / Master of Science

Toksino-antitoksino (TA) sistemos – tai poros viename operone esančių bakterijų ir archėjų genų, kurių vienas koduoja toksišką baltymą, o antras – jį neutralizuojantį baltymą-antitoksiną. Tol, kol ląstelėje gaminamas pakankamas abiejų baltymų kiekis, antitoksinas jungiasi su toksinu ir jį išaktyvina. Tačiau, esant nepalankioms aplinkos sąlygoms, labilesnis antitoksinas suardomas aktyvintų proteazių, o likęs laisvas stabilesnis toksinas slopina gyvybiškai svarbius ląstelinius procesus – baltymų arba DNR biosintezę, dėl ko stabdomas ląstelių augimas arba jos žūva. Escherichia coli chromosomoje aprašyta daugiau nei dešimt TA sistemų, kurių viena yra dinJ-yafQ, apie kurią žinoma labai nedaug. Anksčiau laboratorijoje atliktuose darbuose nustatyta, kad dinJ-yafQ koduoja transliaciją slopinantį toksiną YafQ, o DinJ ir YafQ baltymai sudaro stiprų baltymų kompleksą, slopinantį YafQ toksišką poveikį. Kol kas nieko nėra žinoma apie YafQ molekulės sritis, svarbias sąveikai su antitoksinu DinJ. Šiame darbe sekai atrankios mutagenezės metodu buvo tirtos YafQ baltymo sritys, svarbios sąveikai su „savuoju“ toksinu DinJ. TA sistemoms būdinga savo operono transkripcijos autoreguliacija. DNR sulėtinimo gelyje eksperimentais parodėme atrankią DNR ir antitoksino DinJ bei DinJ-YafQ baltymų komplekso sąveiką. Laisvas antitoksinas DinJ silpniau sąveikauja su DNR nei būdamas komplekse su YafQ, o sąveikai su DNR svarbi DinJ baltymo N galinė dalis. Iš dviejų dinJ-yafQ operono promotoriaus srityje... [toliau žr. visą tekstą] / Prokaryotic toxin antitoxin systems consist of two adjacent genes, where one encodes a stable toxin harmful to essential cellular processes (translation or DNA synthesis), and the other a labile antitoxin, capable of blocking the toxin's activity by binding into stable protein complex. TA systems are proposed to be involved in bacterial adaptation to stress conditions by modulating the level of essential biological processes. There are at least ten characterized chromosome-encoded TA loci in Escherichia coli. The dinJ-yafQ operon codes for YafQ toxin which is neutralized by its cognate antitoxin, DinJ. YafQ is known to inhibit translation in vivo and belongs to the RelE toxin family of toxin ribonucleases. By using site-specific mutagenesis of YafQ, we have investigated the protein regions important for its interaction with DinJ antitoxin. Transcriptional autoregulation has been reported for members of all known TA gene families and appears to be general characteristic of regulation of TA loci. In this work electrophoretic mobility shift assay was used to investigate the interaction between the antitoxin DinJ and DinJ-YafQ complex and dinJ-yafQ operon promoter DNA. Antitoxin DinJ in the complex with YafQ had an enhanced DNA-binding affinity compared to free DinJ. N-terminal domain of antitoxin is crucial for interaction with DNA. Bioinformatic analysis of dinJ-yafQ operon promoter region revealed several palindromic DNA islands and their importance for interaction with DinJ... [to full text]