Transcription factor-associated combinatorial epigenetic pattern reveals higher transcriptional activity of TCF7L2-regulated intragenic enhancers.

Abstract:

BACKGROUND:Recent 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. METHODS:Here, 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. RESULTS:We 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. CONCLUSIONS:Our 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.

journal_name

BMC Genomics

journal_title

BMC genomics

authors

Liu Q,Bonneville R,Li T,Jin VX

doi

10.1186/s12864-017-3764-9

subject

Has Abstract

pub_date

2017-05-12 00:00:00

pages

375

issue

1

issn

1471-2164

pii

10.1186/s12864-017-3764-9

journal_volume

18

pub_type

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