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Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity

Jeehae Park, Javier Estrada, Gemma Johnson, Chiara Ricci-Tam, Meghan Bragdon, Yekaterina Shulgina, Anna Cha, Jeremy Gunawardena, View ORCID ProfileAngela H DePace
doi: https://doi.org/10.1101/408708
Jeehae Park
Harvard Medical School
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Javier Estrada
Harvard Medical School
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Gemma Johnson
Harvard Medical School
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Chiara Ricci-Tam
Harvard Medical School
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Meghan Bragdon
Harvard Medical School
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Yekaterina Shulgina
Harvard Medical School
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Anna Cha
Harvard Medical School
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Jeremy Gunawardena
Harvard Medical School
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Angela H DePace
Harvard Medical School
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  • ORCID record for Angela H DePace
  • For correspondence: angela_depace@hms.harvard.edu
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Abstract

Developmental enhancers integrate graded concentrations of input transcription factors (TFs) to create sharp gene expression boundaries. Here we examine the hunchback P2 (HbP2) enhancer which drives a sharp expression pattern in the Drosophila blastoderm embryo in response to the transcriptional activator Bicoid (Bcd). We systematically interrogate cis and trans factors that influence the shape and position of expression driven by HbP2, and find that the prevailing model, based on cooperative binding of Bcd to HbP2 is not adequate. We demonstrate that other proteins, such as pioneer factors, mediator and histone modifiers influence the shape and position of the HbP2 expression pattern. By comparing our results to theory, we assess how higher-order cooperativity and energy expenditure impact boundary location and sharpness. Our results emphasize that the bacterial view of transcription regulation, where pairwise interactions between regulatory proteins dominate, must be reexamined in animals, where multiple molecular mechanisms collaborate to shape the gene regulatory function.

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Posted September 04, 2018.
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Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity
Jeehae Park, Javier Estrada, Gemma Johnson, Chiara Ricci-Tam, Meghan Bragdon, Yekaterina Shulgina, Anna Cha, Jeremy Gunawardena, Angela H DePace
bioRxiv 408708; doi: https://doi.org/10.1101/408708
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Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity
Jeehae Park, Javier Estrada, Gemma Johnson, Chiara Ricci-Tam, Meghan Bragdon, Yekaterina Shulgina, Anna Cha, Jeremy Gunawardena, Angela H DePace
bioRxiv 408708; doi: https://doi.org/10.1101/408708

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