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Background  Retroviral elements are pervasively transcribed and dynamically regulated during development. While multiple histone- and DNA-modifying enzymes have broadly been associated with their global silencing, little is known about how the many diverse retroviral families are each selectively recognized.    Results  Here we show that the zinc finger protein Krüppel-like Factor 3 (KLF3) specifically silences transcription from the  ORR1A0  long terminal repeat in murine fetal and adult erythroid cells. In the absence of KLF3, we detect widespread transcription from  ORR1A0  elements driven by the master erythroid regulator KLF1. In several instances these aberrant transcripts are spliced to downstream genic exons. One such chimeric transcript produces a novel, dominant negative isoform of PU.1 that can induce erythroid differentiation.    Conclusions  We propose that KLF3 ensures the integrity of the murine erythroid transcriptome through the selective repression of a particular retroelement and is likely one of multiple sequence-specific factors that cooperate to achieve global silencing.

Repression of chimeric transcripts emanating from endogenous retrotransposons by a sequence-specific transcription factor