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Sen. Dan CoatsDaniel (Dan) Ray CoatsIntel heads to resume worldwide threats hearing scrapped under Trump Lack of cyber funds in Biden infrastructure plan raises eyebrows How President Biden can hit a home run MORE (R-Ind.) on Tuesday announced that he will not run for reelection in 2016.

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"Today I am announcing that I will not seek re-election to the United States Senate," Coats said in a statement. "This was not an easy decision. While I believe I am well-positioned to run a successful campaign for another six-year term, I have concluded that the time has come to pass this demanding job to the next generation of leaders."

Coats's decision to retire may set off a Republican scramble for the open seat. While the GOP would seem to have the early edge, it is now another state they must defend in a presidential year where they're almost entirely playing defense to protect their new Senate majority. 

Potential Republican candidates include Reps. Todd YoungTodd Christopher YoungTo encourage innovation, Congress should pass two bills protecting important R&D tax provision Senate Republicans voice opposition to Biden on Iran Biden infrastructure proposal prioritizes funds for emerging technologies MORE and Susan BrooksSusan Wiant BrooksHere are the three GOP lawmakers who voted for the Equality Act Bottom line House Republicans who didn't sign onto the Texas lawsuit MORE, both of whom have long been viewed as having statewide ambitions, as well as Indianapolis Mayor Greg Ballard and Reps. Todd Rokita, Jackie Walorski and Marlin Stutzman.

An aide to Rep. Luke Messer told The Hill he wouldn't seek the Senate seat. 

Coats's chief of staff, Eric Holcomb, is also taking a look at the race and is seen as a top candidate by by Indiana observers. He is close to kingmaker and former Indiana Gov. Mitch Daniels (R), has been traveling the state extensively building connections with the GOP grassroots.

“Eric has taken a leave of absence from Senator Coats’ office as he considers a run for the open U.S. Senate seat in 2016. He’s grateful for the immediate outpouring of support from every corner of Indiana and will make a decision soon,” Pete Seat, a spokesperson for Eric Holcomb, said in a statement.

The seat will be an uphill battle for Democrats. But as President Obama's narrow win in the state in 2008 and Sen. Joe DonnellyJoseph (Joe) Simon DonnellyEverybody wants Joe Manchin Centrist Democrats pose major problem for progressives Biden and Schumer face battles with left if Democrats win big MORE's (D-Ind.) 2012 upset wins attest, Democrats can sometimes compete in the conservative state under the right circumstances.

Their best recruit would likely be former Sen. Evan Bayh (D-Ind.), who chose to retire rather than facing a tough race in 2010 and still has close to $10 million in the bank for a potential return to politics. Bayh has ruled out a run for governor but hasn't closed the door on a Senate run.

National Democrats immediately expressed optimism over the newly open seat, pointing back to their 2012 victory. 

“Indiana's Senate race is now one of the most competitive Senate races in the country, and Democrats are ready to put together a strong campaign just like we did in 2012. We're confident that we will find a great candidate who will put Indiana first and win this seat in 2016," Democratic Senatorial Campaign Committee Chairman Jon TesterJonathan (Jon) TesterThe Hill's Morning Report - Biden's infrastructure plan triggers definition debate Lawmakers say fixing border crisis is Biden's job Five things to watch on Biden infrastructure plan MORE (Mont.) said in a statement. 

If Bayh doesn't run, former Rep. Baron Hill (D-Ind.) and Hammond Mayor Tom McDermott (D) are potential candidates on the Democratic side.

National Republican Senatorial Committee Chairman Roger WickerRoger Frederick WickerBattle lines drawn on Biden's infrastructure plan GOP senator hammers Biden proposal to raise corporate tax rate Sunday shows preview: Democrats eye passage of infrastructure bill; health experts warn of fourth coronavirus wave MORE (Miss.) promised the party will hold the seat next year, touting the state's "strong bench" of Republicans.

“Senator Dan Coats has been a dedicated advocate for Indiana families throughout his time in the United States Senate and I know his devotion to the state he loves so dearly won’t end when he’s out of office," he said in a statement. "Senate Republicans have been blessed to work with such a great colleague over the years and we will miss him dearly. We have a strong Republican bench in Indiana and I am confident we will have another capable Republican joining us in the Senate in 2016 to continue Dan’s great work.”

Coats, 71, has long been thought to be eyeing the exits.

The senator, who'd served in Congress from the 1980s until 2000 and made a comeback to win Bayh's seat in 2010, had been rumored to be tired of Senate gridlock. 

Coats's retirement will open up the chairmanship of the Joint Economic Committee as well as spots on the Senate Finance and Intelligence Committees.

— This post was updated at 1:45 p.m. Scott Wong also contributed.