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

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 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.

journal_name

Genome Biol

journal_title

Genome biology

authors

Mak KS,Burdach J,Norton LJ,Pearson RC,Crossley M,Funnell AP

doi

10.1186/gb-2014-15-4-r58

subject

Has Abstract

pub_date

2014-04-30 00:00:00

pages

R58

issue

4

eissn

1474-7596

issn

1474-760X

pii

gb-2014-15-4-r58

journal_volume

15

pub_type

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