title: PARP1- and CTCF-Mediated Interactions between Active and Repressed Chromatin at the Lamina Promote Oscillating Transcription.
abstract: Transcriptionally active and inactive chromatin domains tend to segregate into separate sub-nuclear compartments to maintain stable expression patterns. However, here we uncovered 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. They not only mediate chromatin fiber interactions but also promote the recruitment of circadian genes to the lamina. Synchronization of the 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 downregulation 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 therefore mediate circadian transcriptional plasticity.
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Honglei
authors: H
authors: Zhao
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Emmanouil G
authors: EG
authors: Sifakis
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Noriyuki
authors: N
authors: Sumida
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Lluís
authors: L
authors: Millán-Ariño
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Barbara A
authors: BA
authors: Scholz
authors: Department of Biosciences and Nutrition, Novum, Karolinska Institutet, 14183 Huddinge, Sweden.
authors: J Peter
authors: JP
authors: Svensson
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Xingqi
authors: X
authors: Chen
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Anna L
authors: AL
authors: Ronnegren
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Carolina Diettrich
authors: CD
authors: Mallet de Lima
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Farzaneh Shahin
authors: FS
authors: Varnoosfaderani
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Chengxi
authors: C
authors: Shi
authors: Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17121 Stockholm, Sweden.
authors: Olga
authors: O
authors: Loseva
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Samer
authors: S
authors: Yammine
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Maria
authors: M
authors: Israelsson
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Li-Sophie
authors: LS
authors: Rathje
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden; Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti út 12, 7624 Pécs, Hungary.
authors: Balázs
authors: B
authors: Németi
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Erik
authors: E
authors: Fredlund
authors: Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17121 Stockholm, Sweden.
authors: Thomas
authors: T
authors: Helleday
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden.
authors: Márta P
authors: MP
authors: Imreh
authors: Department of Microbiology, Tumor and Cell Biology, Nobels väg 16, Karolinska Institutet, 17177 Stockholm, Sweden. Electronic address: anita.gondor@ki.se.
authors: Anita
authors: A
authors: Göndör
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D002940:Circadian Rhythm; D058732:Embryoid Bodies / Q000201:enzymology; D004843:Epistasis, Genetic; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D045325:HCT116 Cells; D000066449:Human Embryonic Stem Cells / Q000201:enzymology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D034881:Nuclear Lamina / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D018797:Cell Cycle Proteins; D002843:Chromatin; C094335:H19 long non-coding RNA; D008565:Membrane Proteins; C509689:PARD3 protein, human; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases