Epigenetic　modifications　are　thought　to　be　important　for　gene　expression　changes　during　HIV-1　transcription　and　replication.　The　removal　of　histone　H3　lysine27　(H3K27)　trimethylation　mark　by　UTX-1　is　important　for　the　robust　induction　of　many　specific　genes　during　Tat-mediated　HIV-1　transactvation.　We　found　that　UTX-1　enzymatic　activity　is　needed　for　Tat　to　remove　a　repressive　mark　H3K27me3　in　the　HIV-1　long　terminal　repeat　(LTR).　UTX-1　converted　the　chromatin　structure　to　a　more　transcriptionally　active　state　by　up-regulation　of　H3K4　methylation　and　down-regulation　of　H3K27　methylation　on　the　specific　regions　of　HIV-1　LTR.　The　increase　in　H3K27me3　and　the　decrease　in　H3K4me3　induced　by　UTX-1　knockdown　was　detected　on　the　HIV-1　LTR,　but　not　by　control　siRNA.　Additionally,　UTX-1　promotes　HIV-1　gene　expression　by　enhancing　both　the　NF-kappa　B　p65＇s　nuclear　translocation　and　its　p65　binding　to　HIV-1　LTR.　And　we　further　demonstrated　that　H3K27　demethylase　activity　was　required　for　increased　HIV-1　transactivation　induced　by　UTX-1.　Together,　our　data　reveal　key　roles　for　UTX-1　in　a　timely　transition　from　poised　to　active　chromatin　in　HIV-1　LTR　during　HIV-1　transcription　and　a　fundamental　mechanism　by　which　a　H3K27　demethylase　triggers　tissue-specific　chromatin　changes.　Our　findings　provide　a　mechanistic　link　between　UTX-1　and　enhanced　HIV-1　replication,　and　suggest　that　targeting　at　epigenetic　mechanism　may　have　a　therapeutic　benefit　for　HIV-1　patients.　(C)　2016　Elsevier　Ltd.　All　rights　reserved.