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PMID: 20413611 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Precise temporal control of the eye regulatory gene Pax6 via enhancer-binding site affinity.

Genes & development ·Vol. 24 ·No. 10 ·2010-05-15 ·Pages 980-5

Rowan S, Siggers T, Lachke SA, Yue Y, Bulyk ML, Maas RL

Abstract

How transcription factors interpret the cis-regulatory logic encoded within enhancers to mediate quantitative changes in spatiotemporally restricted expression patterns during animal development is not well understood. Pax6 is a dosage-sensitive gene essential for eye development. Here, we identify the Prep1 (pKnox1) transcription factor as a critical dose-dependent upstream regulator of Pax6 expression during lens formation. We show that Prep1 activates the Pax6 lens enhancer by binding to two phylogenetically conserved lower-affinity DNA-binding sites. Finally, we describe a mechanism whereby Pax6 levels are determined by transcriptional synergy of Prep1 bound to the two sites, while timing of enhancer activation is determined by binding site affinity.

MeSH Terms
Animals Base Sequence Binding Sites Enhancer Elements, Genetic/genetics Eye Proteins/metabolism Gene Expression Regulation, Developmental Homeodomain Proteins/metabolism Lens, Crystalline/embryology Mice Mice, Inbred C57BL Molecular Sequence Data PAX6 Transcription Factor Paired Box Transcription Factors/metabolism Repressor Proteins/metabolism Sequence Alignment Time Factors
Chemicals
Eye Proteins Homeodomain Proteins PAX6 Transcription Factor Paired Box Transcription Factors Pax6 protein, mouse Pknox1 protein, mouse Repressor Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Rowan Sheldon
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Siggers Trevor
Lachke Salil A
Yue Yingzi
Bulyk Martha L
Maas Richard L
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
1549-5477
DOI
10.1101/gad.1890410
Published
2010-05-15
Epub
2010-00-22
Pages
980-5
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC2867212
Subset
IM
Grants
NEI NIH HHS · R01 EY010123 · United States
NHGRI NIH HHS · R01 HG003985 · United States
CIHR · Canada
NEI NIH HHS · R01 EY10123 · United States
External Links
PubMed source DOI: 10.1101/gad.1890410 PMC Full Text View journal details
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