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Antibody-independent ChIP-sequencing and liver-targeted deletion redefine REVERBα repressor function - ChIP-seq

ABSTRACT: The nuclear receptor REVERBα is a core component of the circadian clock and proposed to be a dominant regulator of hepatic lipid metabolism. We perform in vivo antibody-independent ChIP-sequencing of endogenously-expressed REVERBα, in order to map its cistrome and so define its repressive targets. We find that REVERBα binding sites harbour consensus RORE or RevDR2 motifs, and overlap with corepressor complex binding, without over-representation of putative tethering factors. When Reverbα is deleted in a hepatocyte-selective fashion, only modest physiological and transcriptional effects are seen, with de-repressed target genes tightly associating with REVERBα binding sites. Thus, contrary to previous reports, REVERBα does not repress lipogenesis under basal conditions. REVERBα control of a more extensive transcriptional programme is revealed only by perturbation (the metabolically abnormal global Reverbα-/- mouse, or acutely mistimed feeding), supporting instead a role for this core clock protein in buffering against metabolic challenge.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Mus musculus

SUBMITTER: Rachel Scholey

PROVIDER: E-MTAB-8413 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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| PRJEB37041 | ENA