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.
|Original language||English (US)|
|State||Published - Feb 6 2015|
Bibliographical noteFunding Information:
The authors thank Prof. R. Albert for supplying the network analysis programs and Prof. K. Nakamura for valuable discussions. This study was partly supported by research grants from the Ministry of Education, Culture, Sports, Science and Technology, Japan for RIKEN OSC, CLST and PMI. This work was also supported by the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (Grant Number 26540157).
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