It can be from both. However, it is a bit more tricky when withholding enters the equation. We have a pay-as-you-go system of taxes in the US (essentially payments are required quarterly). If all of your payments are from withholding, they are assumed to be equal across quarters. However, if you make estimated tax payments they are marked as paid when they are actually paid. So, it is possible to meet the 110% safe harbor amount by making one large payment for the 4th quarter, but you could still be hit with an underpayment penalty for the prior three quarters.
