Scoop out some wood filler and push it into any gaps in and around the knot hole with a putty knife. Smooth the surface with the putty knife. Allow it to dry. For large gaps, the wood filler may shrink somewhat. If so, apply it a second time to create a smooth surface. Allow the second application to dry.
Sand the knot hole with a sanding block or use 220-grit sandpaper. Sand the knot hole and surrounding area until you feel no raised points.
Seal the knot hole with a primer-sealer. Use a light coat applied with a paintbrush. The difference between a primer-sealer and regular primer is that the primer-sealer is chemically formulated to be less porous. This protects your final finish more than a regular primer. When the primer-sealer dries, you are ready to paint.