Multiple document comprehension and knowledge integration across domains are particularly important for pre-service teachers, as integrated professional knowledge forms the basis for teaching expertise and competence. This study examines the effects of instructional prompts and relevance prompts embedded in pre-service teachers' learning processes on the quality their knowledge integration in multiple document comprehension across domains. 109 pre-service teachers participated in an experimental study. They read four texts on "competencies" from different knowledge domains and wrote a text on a given scenario. Experimental group 1 was aided with instructional and relevance prompts, while experimental group 2 received only relevance prompts. The control group received no prompting. Perceived relevance of knowledge integration was assessed in a pre-post-test. Pre-service teachers' separative and integrative learning, epistemological beliefs, metacognition, study-specific self-concept, and post-experimental motivation were assessed as control variables. Participants' texts were analyzed concerning knowledge integration by raters and with computer linguistic measures. A key finding is that combined complex prompting enhances pre-service teachers perceived relevance of knowledge integration. This study found effects of prompting types on the pre-service teachers' semantic knowledge structures. Implications for transfer are discussed.