The LPS-induced transcriptional upregulation of the chicken lysozyme locus involves CTCF eviction and noncoding RNA transcription.
Transcription of the lysozyme gene is rapidly induced by proinflammatory stimuli such as treatment with bacterial lipopolysaccharide (LPS). Here we show that this induction involves both the relief of repression mediated by the enhancer-blocking protein CTCF that binds to a negative regulatory element at -2.4 kb, and the activation of two flanking enhancer elements. The downstream enhancer has promoter activity, and LPS stimulation initiates the transient synthesis of a noncoding RNA (LINoCR) transcribed through the -2.4 kb element. Expression of LINoCR is correlated with IKKalpha recruitment, histone H3 phosphoacetylation in the transcribed region, the repositioning of a nucleosome over the CTCF binding site, and, eventually, CTCF eviction. Each of these events requires transcription elongation. Our data reveal a transcription-dependent mechanism of chromatin remodeling that switches a cis-regulatory region from a repressive to an active conformation.
Leeds Institute of Molecular Medicine, University of Leeds, Wellcome Trust Brenner Building, St. James's University Hospital, Leeds LS9 7TF, UK. medple@leeds.ac.uk
Pascal
P
Lefevre
James
J
Witham
Claire E
CE
Lacroix
Peter N
PN
Cockerill
Constanze
C
Bonifer
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002460:Cell Line; D002645:Chickens; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D006657:Histones / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009113:Muramidase / Q000235:genetics*; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics; D050436:Regulatory Elements, Transcriptional; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D000076246:CCCTC-Binding Factor; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006657:Histones; D008070:Lipopolysaccharides; D009707:Nucleosomes; D012333:RNA, Messenger; D022661:RNA, Untranslated; D012097:Repressor Proteins; D012319:RNA Polymerase II; D009113:Muramidase