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Margot Gayle was born in Kansas City, Missouri. The family moved frequently with her father's job, and she attended many different schools during her childhood. She graduated from the University of Michigan and earned a master's degree in bacteriology from Emory University in Atlanta, but had trouble finding a job during the Great Depression. She married William T. Gayle, an accountant, with whom she had two daughters. They moved to New York, where she wrote scripts for CBS Radio. She also worked as a freelance writer and started a public relations business. For 16 years, she wrote an architecture column for The Daily News. In 1957, she ran unsuccessfully for New York City Council.

That year, she began inviting a group of neighbors to her Greenwich Village apartment to discuss how to save the nearby Victorian-Gothic Jefferson Market Courthouse from demolition. Following the outcry over the destruction of Pennsylvania Station, she helped lobby for passage of a landmarks preservation law, which New York City passed in 1965. She founded the Victorian Society in America in 1966 and the Friends of Cast Iron Architecture in 1970. In 1993, she received the Historic Districts Council's Landmarks Lion Award. She was the author of four books, including Cast Iron Architecture in America (1998) with her daughter Carol.
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