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Cell Rep. 2020 Feb 4;30(5):1319-1328.e6. doi: 10.1016/j.celrep.2020.01.006.

Bookmarking by Non-pioneer Transcription Factors during Liver Development Establishes Competence for Future Gene Activation.

Author information

1
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, 70013 Herakleion, Crete, Greece; Biomedical Sciences Research Center Alexander Fleming, 16672 Vari, Greece.
2
Biomedical Sciences Research Center Alexander Fleming, 16672 Vari, Greece.
3
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
4
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, 70013 Herakleion, Crete, Greece. Electronic address: talianid@imbb.forth.gr.

Abstract

Transcription factor binding to enhancer and promoter regions critical for homeostatic adult gene activation is established during development. To understand how cell-specific gene expression patterns are generated, we study the developmental timing of association of two prominent hepatic transcription factors with gene regulatory regions. Most individual binding events display extraordinarily high temporal variations during liver development. Early and persistent binding is necessary, but not sufficient, for gene activation. Stable gene expression patterns are the result of combinatorial activity of multiple transcription factors, which mark regulatory regions long before activation and promote progressive broadening of active chromatin domains. Both temporally stable and dynamic, short-lived binding events contribute to the developmental maturation of active promoter configurations. The results reveal a developmental bookmarking function of master regulators and illuminate remarkable parallels between the principles employed for gene activation during development, during evolution, and upon mitotic exit.

KEYWORDS:

CEBP; HNF4; chromatin; development; gene regulation; liver; transcription factor

Conflict of interest statement

Declaration of Interests The authors declare no competing interests.

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