System-wide analysis of the transcriptional network of human myelomonocytic leukemia cells predicts attractor structure and phorbol-ester-induced differentiation and dedifferentiation transitions.

Sakata K, Ohyanagi H, Sato S, Nobori H, Hayashi A, Ishii H, Daub CO, Kawai J, Suzuki H, Saito T

Sci Rep 5 (-) 8283 [2015-02-06; online 2015-02-06]

We present a system-wide transcriptional network structure that controls cell types in the context of expression pattern transitions that correspond to cell type transitions. Co-expression based analyses uncovered a system-wide, ladder-like transcription factor cluster structure composed of nearly 1,600 transcription factors in a human transcriptional network. Computer simulations based on a transcriptional regulatory model deduced from the system-wide, ladder-like transcription factor cluster structure reproduced expression pattern transitions when human THP-1 myelomonocytic leukaemia cells cease proliferation and differentiate under phorbol myristate acetate stimulation. The behaviour of MYC, a reprogramming Yamanaka factor that was suggested to be essential for induced pluripotent stem cells during dedifferentiation, could be interpreted based on the transcriptional regulation predicted by the system-wide, ladder-like transcription factor cluster structure. This study introduces a novel system-wide structure to transcriptional networks that provides new insights into network topology.

Affiliated researcher

PubMed 25655563

DOI 10.1038/srep08283

Crossref 10.1038/srep08283

pii: srep08283
pmc: PMC4319166

Publications 7.1.2