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

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

Volume: 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

Affiliation:

• Recombinant Proteins Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad,Iran

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

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.

Cite this article as:

Nazanin Gholampour-Faroji , Aliakbar Haddad-Mashadrizeh *, Mahdi Mirahmadi , Hassan Monhemi , Safoora Shahreki-Mojahed, Reza Ahmad Bahrami , Mohammadreza Housaindokht , Maryam M. Matin , Alireza Zomorodipour , Parisa Dadjoo and Mahdi Nohtani , In-silico Evidences of Regulatory Roles of WT1 Transcription Factor Binding Sites on the Intervening Sequences of the Human Bcl-2 Gene, Current Bioinformatics 2018; 13 (3) . https://dx.doi.org/10.2174/1574893612666170428114551