You need to prime with a primer that blocks "tannin bleed" - that's what it's called when the knotholes bleed through. The best primer for that is Zinsser BIN, which is shellac based. It smells bad so be sure you have lots of ventilation when you start painting with it. What I would do is lightly sand and wash the walls as usual to prep them. Then get a couple disposable brushes (BIN is hard to clean up so I usually just toss the brushes) - don't use foam because they dissolve in the BIN. Just spot prime over the knotholes - use 2 or 3 coats - BIN dries fast (~15 minutes) so by the time you are all the way around the room, you can just start the next coat. Try to feather the edges and blend it so you don't have a big splotch right over the knothole. Then you can either prime the whole wall with regular water-based primer then paint or just go right to painting (if you skip the primer, you may be able to see the spot-primed spots, depending on what you use and how many coats of the final paint, so a PRO would definitely prime the whole wall first. Me, I'm lazy, and I might try to get by with just the topcoat....)

Good luck!

Thanks, lkp. Fortunately, it's just a small bathroom so I'll probably reprime the whole room.