Trenzalore was a place that, according to Dorium Maldovar, the Doctor would visit at some point in his travels, which would coincide with 'the Fall of the Eleventh'. He told the Doctor that at this time and place 'no living creature can speak falsely or fail to answer.' Here, the First Question in the universe would be asked.
The Silence were determined that the Doctor never reach Trenzalore, so that the question would never be answered. It was a creed of the Silence that 'Silence will fall when the Question is asked', or as Maldovar translated it, 'Silence must fall when the question is asked'. (DW: The Wedding of River Song)