Gene network transitions in embryos depend upon interactions between a pioneer transcription factor and core histones

• Published in: Nature genetics Vol. 52; no. 4; pp. 418 - 427
• Main Authors: Iwafuchi, Makiko, Cuesta, Isabel, Donahue, Greg, Takenaka, Naomi, Osipovich, Anna B., Magnuson, Mark A., Roder, Heinrich, Seeholzer, Steven H., Santisteban, Pilar, Zaret, Kenneth S.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2020; Nature Publishing Group
• Subjects: 38; 38/35; 38/39; 38/91; 45; 631/136; 631/208; 631/337; 631/532; 64; 64/60; 82; 82/80; Agriculture; Amino Acid Sequence; Amino acids; Animal Genetics and Genomics; Animals; Arrays; Binding sites; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Line; Chromatin; Chromatin - genetics; Deoxyribonucleic acid; DNA; DNA - genetics; Embryonic development; Embryos; Female; Gene Expression Regulation, Developmental - genetics; Gene Function; Gene Regulatory Networks - genetics; Genetic algorithms; Genetic aspects; Histones; Histones - genetics; Human Genetics; Humans; Mice; Mice, Inbred C57BL; Molecular interactions; Mutation; Nucleosomes - genetics; Peptides; Physiological aspects; Proteins; Transcription factors; Transcription Factors - genetics; Transcription, Genetic - genetics; United States
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/s41588-020-0591-8

Gene network transitions in embryos and other fate-changing contexts involve combinations of transcription factors. A subset of fate-changing transcription factors act as pioneers; they scan and target nucleosomal DNA and initiate cooperative events that can open the local chromatin. However, a gap has remained in understanding how molecular interactions with the nucleosome contribute to the chromatin-opening phenomenon. Here we identified a short α-helical region, conserved among FOXA pioneer factors, that interacts with core histones and contributes to chromatin opening in vitro. The same domain is involved in chromatin opening in early mouse embryos for normal development. Thus, local opening of chromatin by interactions between pioneer factors and core histones promotes genetic programming. An α-helical region conserved among FOXA pioneer factors interacts with core histones and promotes chromatin opening in vitro. This region also promotes chromatin opening in early mouse embryos and is required for normal development.