Journal
NATURE GENETICS
Volume 41, Issue 5, Pages 553-562Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.375
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Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- RIKEN Frontier Research System, Functional RNA research program
- Australian National Health and Medical Research Council [ID 428261]
- SNF [SNF 3100A0-118318]
- MRC [MC_U105161047] Funding Source: UKRI
- Medical Research Council [MC_U105161047, G9900991B] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [21570151] Funding Source: KAKEN
- Fondazione Telethon Funding Source: Custom
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Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites, we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process.
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