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Plans for a European super league would be "very damaging" for football and "we support football authorities in taking action", Boris Johnson has said.
The prime minister tweeted that the proposals "would strike at the heart of the domestic game, and will concern fans across the country".
He added: "The clubs involved must answer to their fans and the wider footballing community before taking any further steps."
Six English teams are expected to be part of plans for the breakaway European super league, with an announcement due soon, Sky News understands.
Among the English clubs involved are Liverpool, Manchester United, Arsenal and Chelsea.
Sky News' City editor Mark Kleinman said: "My understanding is that 12 clubs from across Europe including the six biggest English clubs have now signed up to this new format.
"The others include Barcelona, Juventus and Real Madrid."
The project is being launched to rival UEFA's Champions League format which currently dominates European football.
The developments come as UEFA itself was due to sign off on its own plans for an expanded and restructured Champions League on Monday.
UEFA, the FA, and the Premier League - as well as football authorities in Spain and Italy - have expressed their opposition to a breakaway European super league.
In a joint statement they said they "remain united in our efforts to stop this cynical project", adding: "We thank those clubs in other countries, especially the French and German clubs, who have refused to sign up to this.
"This persistent self-interest of a few has been going on for too long. Enough is enough."
The Premier League's chief executive Richard Masters has written to all 20 clubs in England's top division to state that "this venture cannot be launched without English clubs and we call upon any club contemplating associating themselves or joining this venture to walk away immediately before irreparable damage is done".
The English FA said the move would be "damaging to English and European football at all levels" and that it would "attack the principles of open competition and sporting merit which are fundamental to competitive sport".
It's statement added: "We would not provide permission to any competition that would be damaging to English football, and will take any legal and/or regulatory action necessary to protect the broader interests of the game."
Speaking about the developments, former Manchester United defender Gary Neville told Sky Sports: "I'm not against the modernisation of football competitions, we have the Premier League, the Champions League, but I think to bring forward proposals in the midst of COVID and the economic crisis for all clubs is an absolute scandal.
"United and the rest of the 'Big Six' that have signed up to it against the rest of the Premier League should be ashamed of themselves."
Neville added: "They should deduct six points off all six teams that have signed up to it. Deduct points off them all. To do it during a season? It's a joke."
The move to create a rival league is being seen by some in football as a surprise after the European Club Association (ECA), which represents 246 of the continent's leading clubs, gave its backing to UEFA's reforms.
UEFA has proposed an increase to 36 from 32 teams in the Champions League, and an overhaul of the group stage into a single table rather than the current groups of four clubs.
Teams would play 10 matches each in the group stage rather than the six they currently play and a playoff round would also be introduced before the last 16.
There have been reports of a plan for a breakaway league for a number of years and the speculation returned in January with several media reports that a document had been produced outlining the plans for a 20-team league.
Those reports led FIFA and UEFA to warn they would ban any players involved in a breakaway from playing in the World Cup or European Championship.