The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line
We analyzed transcriptional control in the human monocytic cell line THP-1 throughout a time course of differentiation. A new deep sequencing technology (deepCAGE) together with microarray analysis provided an integrated picture of promoter (deepCAGE) and mRNA expression over time. Comparative genomic regulatory site prediction and modeling the activities of regulatory motifs through time identified the key transcription factors driving differentiation, their time-dependent activities, and their target genes. Systematic siRNA knockdown of 52 key transcription factors confirmed the role of individual factors in the differentiation process. This analysis has therefore mapped a suite of transcription factors required for the maintenance of the undifferentiated state and for the transition from proliferation to differentiation.
The human monocytic cell line THP-1 throughout a time course of differentiation was profiled by deepCAGE together with microarray and ChIP/chip analysis. Systematic siRNA knockdown of 52 key transcription factors are perfomed, with following micorarray analysis.