She was born in Canada, her family having emigrated from Haiti during the dictatorship of Jean-Claude Duvalier, and she grew up in St-Lambert, across from Montreal. She is a dual Canadian-American citizen. Her heritage is alluded to in the Arcade Fire song "Haiti", in which she sings, Mes cousins jamais nés hantent les nuits des Duvalier ("My never-born cousins haunt the nights of the Duvaliers").
Chassagne earned a B.A. in communication studies at Concordia University in 1998, and went on to study jazz voice briefly at McGill University. She was singing jazz at an art opening at Concordia in 2000 when Butler met her and persuaded her to join his band; after line-up changes, only the two of them were left. They married in 2003. She plays many instruments on stage, including the accordion, drums, the xylophone, hurdy-gurdy, keyboards and organ.
Chassagne has also been involved with a medieval band called Les Jongleurs de la Mandragore, and a jazz band, Azúcar. She also wrote the music for the two-minute David Uloth sketch: "The Shine, and contributed to the UNICEF benefit project as part the North American Hallowe'en Prevention Initiative, performing the song "Do They Know It's Hallowe'en?" along with Win Butler.
On several occasions Regine has launched into her song "Haiti" with an anecdote regarding her love of roses. This is her username on the Arcade Fire fansite.