PARP1- and CTCF-mediated interactions between active and repressed chromatin at the lamina promote oscillating transcription. Homo sapiens

Transcriptionally active and inactive chromatin domains tend to segregate into separate sub-nuclear compartments to maintain stable expression patterns. However, we have uncovered here an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains (LADs). The interactome is regulated by PARP1 and its co-factor, CTCF, which not only mediate chromatin fiber interactions, but also promote the recruitment of circadian genes to the lamina. Synchronization of circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. Furthermore, depletion of H3K9me2/3, inhibition of PARP activity by Olaparib or down-regulation of PARP1 or CTCF expression counteracts both recruitment to the envelope and circadian transcription. PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina thus mediate circadian transcriptional plasticity. Overall design: ChIP-Seq for H3k9me2 in HCT116 colon cancer cells (2 replicates)