Developmental Role and Mechanistic Insight into Chromatin Opening by Pioneer Factor FoxA Center for Developmental Biology

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Category	Seminar
Date and Time	2017-09-13 16:00 - 17:00
Venue	Seminar Room A7F
Speaker	Makiko Iwafuchi-Doi
Affiliation	University of Pennsylvania, Perelman School of Medicine
Title	Developmental Role and Mechanistic Insight into Chromatin Opening by Pioneer Factor FoxA
Poster	click here to download(PDF)
Host	Mitsuru Morimoto
Summary	Gene regulation occurs in the context of chromatin, the complex of DNA and histone proteins that makes up nucleosomes, where linker histones stabilize a repressive, closed configuration. A distinct combination of transcription factors is necessary to elicit cell fate changes in embryonic development and cellular reprogramming. Within each group of fate-changing transcription factors, a subset called “pioneer factors” are dominant in their ability to engage silent chromatin and recruit other transcription factors, thereby imparting a new function to regulatory DNA sequences. However, the molecular mechanisms by which pioneer factors open chromatin remains unclear. Here we demonstrate that a pioneer factor FoxA, but not ATP-dependent chromatin remodelers, opens chromatin compacted with linker histones, which then allows chromatin remodelers to further open chromatin. We identified a chromatin opening domain in FoxA C-terminus that potentially interacts with core histones. When we deleted the chromatin opening domain in the mouse FoxA2 genomic locus, but kept the other FoxA2 parts intact, including the DNA binding and transactivation domains, chromatin opening and embryonic development were markedly affected. These studies provide mechanistic insight into chromatin opening and can ultimately enhance our ability to control chromatin state at will. Zaret KS, Lerner J, Iwafuchi-Doi M. Chromatin Scanning by Dynamic Binding of Pioneer Factors. Mol Cell. 2016 Jun 2;62(5):665-7. Review. Iwafuchi-Doi M, Donahue G, Kakumanu A, Watts JA, Mahony S, Pugh BF, Lee D,Kaestner KH, Zaret KS. The Pioneer Transcription Factor FoxA Maintains an Accessible Nucleosome Configuration at Enhancers for Tissue-Specific Gene Activation. Mol Cell. 2016 Apr 7;62(1):79-91.