Peak-valley-peak pattern of histone modifications delineates active regulatory elements and their directionality.
Formation of nucleosome free region (NFR) accompanied by specific histone modifications at flanking nucleosomes is an important prerequisite for enhancer and promoter activity. Due to this process, active regulatory elements often exhibit a distinct shape of histone signal in the form of a peak-valley-peak (PVP) pattern. However, different features of PVP patterns and their robustness in predicting active regulatory elements have never been systematically analyzed. Here, we present PARE, a novel computational method that systematically analyzes the H3K4me1 or H3K4me3 PVP patterns to predict NFRs. We show that NFRs predicted by H3K4me1 and me3 patterns are associated with active enhancers and promoters, respectively. Furthermore, asymmetry in the height of peaks flanking the central valley can predict the directionality of stable transcription at promoters. Using PARE on ChIP-seq histone modifications from four ENCODE cell lines and four hematopoietic differentiation stages, we identified several enhancers whose regulatory activity is stage specific and correlates positively with the expression of proximal genes in a particular stage. In conclusion, our results demonstrate that PVP patterns delineate both the histone modification landscape and the transcriptional activities governed by active enhancers and promoters, and therefore can be used for their prediction. PARE is freely available at http://servers.binf.ku.dk/pare.
The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, 2200 Copenhagen, Denmark Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark.
Sachin
S
Pundhir
The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, 2200 Copenhagen, Denmark Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark.
Frederik O
FO
Bagger
The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, 2200 Copenhagen, Denmark Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Felicia B
FB
Lauridsen
The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, 2200 Copenhagen, Denmark Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark.
Nicolas
0000-0001-5208-8874
N
Rapin
The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, 2200 Copenhagen, Denmark Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark bo.porse@finsenlab.dk.
Bo T
BT
Porse
D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D006367:HeLa Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology; D056945:Hep G2 Cells; D042421:Histone Code / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009707:Nucleosomes / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015533:Transcriptional Activation
D006657:Histones; D009707:Nucleosomes