GSE26880
PARP1- and CTCF-mediated interactions between active and repressed chromatin at the lamina promote oscillating transcription
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: Examination of intra- and interchromosomal interactions in human embryonic stem cells (HESCs) and derived embryoid bodies (HEBs) generated by 4C-seq, as described in (Zhao et al., 2006), using Illumina Genome Analyzer II and Illumina MiSeq. Examination of mRNA profiles in HESCs and derived HEBs generated by deep sequencing, in duplicate, using Illumina HiSeq 2500.