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In-silico Evidences of Regulatory Roles of WT1 Transcription Factor Binding Sites on the Intervening Sequences of the Human Bcl-2 Gene

[ Vol. 13 , Issue. 3 ]

Author(s):

Gholampour-Faroji Nazanin, Haddad-Mashadrizeh Aliakbar*, Mirahmadi Mahdi, Monhemi Hassan, Shahreki-Mojahed Safoora, Bahrami Ahmad Reza, Housaindokht Mohammadreza, Matin M. Maryam, Zomorodipour Alireza, Dadjoo Parisa and Nohtani Mahdi   Pages 260 - 272 ( 13 )

Abstract:


Background: Intervening sequences (introns) have significant effects on genomic regulations and molecular evolution. So, it deserves a deeper analysis for better understanding the possible regulatory roles of these regions.

Objective and Method: Accordingly, the intron 2 (In-2) of the human B-cell lymphoma 2 (hBcl2) gene, with regard to the size of the In-2 as well as critical roles of the gene in the homeostatic of the cellular balance, was analyzed by using in-silico approaches to identify In-2 transcription factor binding (In2-TFBs) motifs.

Results: Our analysis revealed 966 motifs of 118 different TFBs types which were scattered throughout both the strands of the complete sequence of the gene, in particular on the In-2, with significant pattern of distribution and repetition. Distribution pattern of these motifs revealed that most of them were accumulated in narrow regions of the In-2, far from the area of the splicing sites. Moreover, it was observed that except for WT1-TFBs, Gfi-1-TFBs, GAGA-TFBs, all other motifs were sporadic, with irregular and random distribution. Among these motifs, WT1-TFBs showed the highest frequencies which were situated in four neighboring regions of the In-2, by a close linear relationship to Sp1-TFBs. Furthermore, the sequence logos of the WT1-TFBs showed that they ranged in size from 22 up to 45 bps and were enriched with G and T nucleotides. Meanwhile, the binding affinity of WT1-TF to WT1- TFBs revealed significant differences compared to the other sequences of the gene as negative control.

Conclusion: In general, this data provides supporting evidences for the existence of regulatory regions in the intronic sequences of the hBcl2 gene especially in the In-2, and also represents new targets for WT1-TF which might contribute to hBcl2 regulation and apoptosis process.

Keywords:

hBcl2 gene, intron, gene regulation, TFBs, WT1.

Affiliation:

Recombinant Proteins Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Recombinant Proteins Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Department of Cancer Research, Nastaran Center for Cancer Prevention (NCCP), Mashhad, Structural Biology and Bioinformatics Research Group, Khayyam Bioeconomy Institute (KBI), Mashhad, Structural Biology and Bioinformatics Research Group, Khayyam Bioeconomy Institute (KBI), Mashhad, Recombinant Proteins Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Recombinant Proteins Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, National Institute for Genetic Engineering and Biotechnology, Tehran, Structural Biology and Bioinformatics Research Group, Khayyam Bioeconomy Institute (KBI), Mashhad, Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad

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