UH regents sounded off with a series of "Aye!" votes to allow chancellor Renu Khator to negotiate a new conference home for Cougar athletics.
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The chairman of the board of regents, Tilman Fertitta, said, "We're all proud to be Cougars today."
Tuesday's vote to move forward comes five years after the one-time powerhouse league refused to invite UH.
UH is now expected to join Brigham Young University, the University of Central Florida and the University of Cincinnati in a new Big 12 after the University of Texas and Oklahoma decided to move to the SEC.
A formal invitation from the conference is expected to come in a matter of days. The invited schools could become members by 2023 or 2024, depending on when UT and OU exit for their new conference home.
The Big 12 also has Baylor University, Iowa State, the University of Kansas, Kansas State, Oklahoma State University, Texas Christian University, Texas Tech, and West Virginia.
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Houston is currently part of the American Athletic Conference, and if the school chooses to leave, would have to pay a $10 million exit fee.
The implications for UH could mean the school sharing into lucrative TV rights revenue. In the last fiscal year, each Big 12 school reportedly earned up to $40.5 million in revenue.
In comparison, a school in the American Athletic Conference earned on average almost $7 million from TV rights revenue.
Will UH join the Big 12? Here's how fans feel about it
Will UH join the Big 12? Here's how fans feel about it