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Open Access Highly Accessed Research

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

Ka Sin Mak, Jon Burdach, Laura J Norton, Richard CM Pearson, Merlin Crossley* and Alister PW Funnell

Author Affiliations

School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington NSW 2052, Australia

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Genome Biology 2014, 15:R58  doi:10.1186/gb-2014-15-4-r58

Published: 30 April 2014

Abstract

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 Kr├╝ppel-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.

Keywords:
Retrotransposons; Chimeric transcripts; KLF1; KLF3; KLFs; Gene regulation; Erythroid; Transcription factors