TY - JOUR
T1 - Discriminative identification of transcriptional responses of promoters and enhancers after stimulus
AU - Kleftogiannis, Dimitrios A.
AU - Kalnis, Panos
AU - Arner, Erik
AU - Bajic, Vladimir B.
N1 - KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: King Abdullah University of Science and Technology (KAUST); Research Grant from MEXT [to the RIKEN Center for Life Science Technologies]. Funding for open access charge: King Abdullah University of Science and Technology (KAUST).
PY - 2016/10/26
Y1 - 2016/10/26
N2 - Promoters and enhancers regulate the initiation of gene expression and maintenance of expression levels in spatial and temporal manner. Recent findings stemming from the Cap Analysis of Gene Expression (CAGE) demonstrate that promoters and enhancers, based on their expression profiles after stimulus, belong to different transcription response subclasses. One of the most promising biological features that might explain the difference in transcriptional response between subclasses is the local chromatin environment. We introduce a novel computational framework, PEDAL, for distinguishing effectively transcriptional profiles of promoters and enhancers using solely histone modification marks, chromatin accessibility and binding sites of transcription factors and co-activators. A case study on data from MCF-7 cell-line reveals that PEDAL can identify successfully the transcription response subclasses of promoters and enhancers from two different stimulations. Moreover, we report subsets of input markers that discriminate with minimized classification error MCF-7 promoter and enhancer transcription response subclasses. Our work provides a general computational approach for identifying effectively cell-specific and stimulation-specific promoter and enhancer transcriptional profiles, and thus, contributes to improve our understanding of transcriptional activation in human.
AB - Promoters and enhancers regulate the initiation of gene expression and maintenance of expression levels in spatial and temporal manner. Recent findings stemming from the Cap Analysis of Gene Expression (CAGE) demonstrate that promoters and enhancers, based on their expression profiles after stimulus, belong to different transcription response subclasses. One of the most promising biological features that might explain the difference in transcriptional response between subclasses is the local chromatin environment. We introduce a novel computational framework, PEDAL, for distinguishing effectively transcriptional profiles of promoters and enhancers using solely histone modification marks, chromatin accessibility and binding sites of transcription factors and co-activators. A case study on data from MCF-7 cell-line reveals that PEDAL can identify successfully the transcription response subclasses of promoters and enhancers from two different stimulations. Moreover, we report subsets of input markers that discriminate with minimized classification error MCF-7 promoter and enhancer transcription response subclasses. Our work provides a general computational approach for identifying effectively cell-specific and stimulation-specific promoter and enhancer transcriptional profiles, and thus, contributes to improve our understanding of transcriptional activation in human.
UR - http://hdl.handle.net/10754/622038
UR - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkw1015
UR - http://www.scopus.com/inward/record.url?scp=85030613388&partnerID=8YFLogxK
U2 - 10.1093/nar/gkw1015
DO - 10.1093/nar/gkw1015
M3 - Article
C2 - 27789687
SN - 0305-1048
VL - 45
SP - gkw1015
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 4
ER -