'Traffic light rules': Chromatin states direct miRNA-mediated network motifs running by integrating epigenome and regulatome.
BACKGROUND
Epigenetic marks can cooperatively regulate chromatin accessibility and in turn facilitate or impede the binding of regulatory factors to various elements, suggesting their important roles in regulatory circuits. However, it remains elusive as to how epigenetic marks cooperate in the operations of regulatory network.


METHODS
Here, we systematically characterized chromatin states of 26 epigenetic marks on different elements of protein-coding genes and miRNAs. We comprehensively analyzed, by using an integrative regulatory network, how cooperation among epigenetic, transcriptional, and post-transcriptional regulations came about.


RESULTS
We observed extensive cooperation of epigenetic marks on local functional elements and complex epigenetic patterns corresponding to different biological functions. By identifying the significantly epigenetic state-modified motifs, we found that multiple combinations of epigenetic states were associated with a specific type of motif. Interestingly, miRNA-mediated motifs were linked to stable epigenetic states of downstream targets. Changes in epigenetic states of downstream targets in miRNA-mediated motifs can buffer the effects of upstream regulator on target genes, suggesting that miRNA-mediated motifs require the cooperation of epigenetic marks.


CONCLUSIONS
Overall, epigenetic marks are involved in the running of regulatory motifs in the way traffic lights control traffic flows and hence should be part of the architecture of complex regulatory circuits.


CONCLUSIONS
We demonstrated a detailed analysis of the cooperation of multiple epigenetic marks and how epigenetic regulation was organized into a human regulatory network. The findings form a basis for further understanding of the complicated roles of epigenetic marks on regulatory circuits.
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Hongying
H
Zhao
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Guanxiong
G
Zhang
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Lin
L
Pang
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Yujia
Y
Lan
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Li
L
Wang
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Fulong
F
Yu
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Jing
J
Hu
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Feng
F
Li
Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
Tingting
T
Zhao
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China; Key Laboratory of Cardiovascular Medicine Research, Harbin Medical University, Ministry of Education, Harbin, China. Electronic address: xiaoyun@ems.hrbmu.edu.cn.
Yun
Y
Xiao
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China. Electronic address: lixia@hrbmu.edu.cn.
Xia
X
Li
D001665:Binding Sites; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D019295:Computational Biology; D030541:Databases, Genetic; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012323:RNA Processing, Post-Transcriptional; D013597:Systems Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D002843:Chromatin; D006657:Histones; D035683:MicroRNAs; D014157:Transcription Factors
Chromatin states; Epigenetic regulation; Post-transcriptional regulation;; Transcriptional regulation; miRNA; miRNA-mediated network motifs