Authors:
Bich Hai Ho
;
Ngoc Tu Le
and
Tu Bao Ho
Affiliation:
Japan Advanced Institute of Science and Technology, Japan
Keyword(s):
Nucleosome dynamics, Bayesian network, Post-translational histone modification, Transcriptional regulator.
Related
Ontology
Subjects/Areas/Topics:
Bioinformatics
;
Biomedical Engineering
;
Data Mining and Machine Learning
;
Genomics and Proteomics
Abstract:
Intergenic regions are unstable, owing to trans-regulatory factors that regulate chromatin structure. Nucleosome
organization at promoter has been shown to exhibit distinct patterns corresponding to the level of gene
expression. Post-translational modifications (PTMs) of histone proteins and transcriptional regulators, including
chromatin remodeling complexes (CRCs), general transcription factors (GTFs), and RNA polymerase II
(PolII), are presumably related to the establishment of such nucleosome dynamics. However, their concrete
relationships, especially in gene regulation, remain elusive. We, therefore, sought to understand the functional
linkages among these factors and nucleosome dynamics by deriving a Bayesian network (BN)-based model
representing their interactions. Based on the recovered network, learnt from 8 PTMs and 15 transcriptional
regulators at 4034 S.cerevisiae promoters, we speculate that nucleosome organization at promoter is intentionally
volatile in various regulat
ory pathways. Notably, interactions of CRCs/GTFs and H3 histone methylation
were inferred to co-function with nucleosome dynamics in gene repression and pre-initiation complex (PIC)
formation. Our results affirm the hypothesis that extrinsic factors take part in regulating nucleosome dynamics.
More thorough investigation can be made by adding more factors and using our proposed method.
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