Transcription factor-associated combinatorial epigenetic pattern reveals higher transcriptional activity of TCF7L2-regulated intragenic enhancersReportar como inadecuado




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BMC Genomics

, 18:375

Human and rodent genomics

Abstract

BackgroundRecent studies have suggested that combinations of multiple epigenetic modifications are essential for controlling gene expression. Despite numerous computational approaches have been developed to decipher the combinatorial epigenetic patterns or -epigenetic code-, none of them has explicitly addressed the relationship between a specific transcription factor TF and the patterns.

MethodsHere, we developed a novel computational method, T-cep, for annotating chromatin states associated with a specific TF. T-cep is composed of three key consecutive modules: i Data preprocessing, ii HMM training, and iii Potential TF-states calling.

ResultsWe evaluated T-cep on a TCF7L2-omics data. Unexpectedly, our method has uncovered a novel set of TCF7L2-regulated intragenic enhancers missed by other software tools, where the associated genes exert the highest gene expression. We further used siRNA knockdown, Co-transfection, RT-qPCR and Luciferase Reporter Assay not only to validate the accuracy and efficiency of prediction by T-cep, but also to confirm the functionality of TCF7L2-regulated enhancers in both MCF7 and PANC1 cells respectively.

ConclusionsOur study for the first time at a genome-wide scale reveals the enhanced transcriptional activity of cell-type-specific TCF7L2 intragenic enhancers in regulating gene expression.

KeywordsT-cep TCF7L2 Intragenic enhancer PANC1 MCF7 Electronic supplementary materialThe online version of this article doi:10.1186-s12864-017-3764-9 contains supplementary material, which is available to authorized users.





Autor: Qi Liu - Russell Bonneville - Tianbao Li - Victor X. Jin

Fuente: https://link.springer.com/







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