Building Promoter Aware Transcriptional Regulatory Networks Using SiRNA Perturbation and DeepCAGE
Overview
Authors
Affiliations
Perturbation and time-course data sets, in combination with computational approaches, can be used to infer transcriptional regulatory networks which ultimately govern the developmental pathways and responses of cells. Here, we individually knocked down the four transcription factors PU.1, IRF8, MYB and SP1 in the human monocyte leukemia THP-1 cell line and profiled the genome-wide transcriptional response of individual transcription starting sites using deep sequencing based Cap Analysis of Gene Expression. From the proximal promoter regions of the responding transcription starting sites, we derived de novo binding-site motifs, characterized their biological function and constructed a network. We found a previously described composite motif for PU.1 and IRF8 that explains the overlapping set of transcriptional responses upon knockdown of either factor.
Aznaourova M, Schmerer N, Janga H, Zhang Z, Pauck K, Bushe J Proc Natl Acad Sci U S A. 2022; 119(36):e2120680119.
PMID: 35998224 PMC: 9457492. DOI: 10.1073/pnas.2120680119.
Selective Activation of Alternative Core Promoters by Wnt-Responsive Enhancers.
Bardales J, Wieser E, Kawaji H, Murakawa Y, Darzacq X Genes (Basel). 2018; 9(6).
PMID: 29882899 PMC: 6027352. DOI: 10.3390/genes9060270.
Gao N, Ud-Dean S, Gandrillon O, Gunawan R Bioinformatics. 2017; 34(2):258-266.
PMID: 28968704 PMC: 5860204. DOI: 10.1093/bioinformatics/btx575.
Lizio M, Ishizu Y, Itoh M, Lassmann T, Hasegawa A, Kubosaki A Front Genet. 2015; 6:331.
PMID: 26635867 PMC: 4650373. DOI: 10.3389/fgene.2015.00331.
RNA sequencing: from tag-based profiling to resolving complete transcript structure.
de Klerk E, den Dunnen J, t Hoen P Cell Mol Life Sci. 2014; 71(18):3537-51.
PMID: 24827995 PMC: 4143603. DOI: 10.1007/s00018-014-1637-9.