Bookmarking by Non-pioneer Transcription Factors during Liver Development Establishes Competence for Future Gene Activation
| Autor: | Panagiotis Moulos, Panagiota Karagianni, Dominic Schmidt, Duncan T. Odom, Iannis Talianidis |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Transcriptional Activation CEBP Biology Regulatory Sequences Nucleic Acid liver General Biochemistry Genetics and Molecular Biology Article HNF4 03 medical and health sciences 0302 clinical medicine Gene expression Animals Humans Gene Silencing Enhancer Gene Transcription factor development lcsh:QH301-705.5 transcription factor Regulation of gene expression Mice Knockout Developmental maturation Bookmarking CCAAT-Enhancer-Binding Protein-beta Gene Expression Regulation Developmental Chromatin Cell biology Mice Inbred C57BL 030104 developmental biology Hepatocyte Nuclear Factor 4 lcsh:Biology (General) Regulatory sequence gene regulation 030217 neurology & neurosurgery Protein Binding Transcription Factors |
| Zdroj: | Cell Reports, Vol 30, Iss 5, Pp 1319-1328.e6 (2020) Cell Reports |
| ISSN: | 2211-1247 |
| Popis: | Summary 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. Graphical Abstract Highlights • HNF4α and C/EBPα binding are highly dynamic during development • HNF4α and C/EBPα bookmark target genes for future activation • Stable and transient binding of multiple factors is required for transcription • Dynamic binding events facilitate the formation of broad open chromatin domains Karagianni et al. show that during liver development, master transcription factors bind to their targets in a temporally stable or dynamic manner. Transcription factors mark regulatory regions long before gene activation. Commonalities among the mechanisms of gene activation during development, evolution, and mitotic exit are described. |
| Databáze: | OpenAIRE |
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