Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization

Cell
Elphège P NoraBenoit G Bruneau

Abstract

The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and insulation of topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding. CTCF remains essential for TAD organization in non-dividing cells. Surprisingly, active and inactive genome compartments remain properly segregated upon CTCF depletion, revealing that compartmentalization of mammalian chromosomes emerges independently of proper insulation of TADs. Furthermore, our data support that CTCF mediates transcriptional insulator function through enhancer blocking but not as a direct barrier to heterochromatin spreading. Beyond defining the functions of CTCF in chromosome folding, these results provide new fundamental insights into the rules governing mammalian genome organization.

Citations

May 4, 2017·ELife·Anders S HansenXavier Darzacq
Jun 3, 2017·Development, Growth & Differentiation·Takeshi Sugawara, Akatsuki Kimura
Jun 13, 2017·Nature Methods·Geoffrey Fudenberg, Maxim Imakaev
Jan 6, 2018·Cellular and Molecular Life Sciences : CMLS·Joyce ManVincent M Christoffels
Oct 5, 2017·Human Molecular Genetics·A Marieke OudelaarDouglas R Higgs
Jan 24, 2018·International Journal of Molecular Sciences·François Le Dily, Miguel Beato
Oct 5, 2017·Nucleic Acids Research·Ravi BoyaJagan M R Pongubala
Apr 9, 2018·Biochemistry. Biokhimii︠a︡·S V Razin, A A Gavrilov
Jan 20, 2018·Science·Johan H GibcusJob Dekker
Nov 18, 2017·Annual Review of Immunology·Charles R M Bangham
Apr 18, 2018·Nature Genetics·Simona BiancoMario Nicodemi
Aug 10, 2017·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Sergey V UlianovSergey V Razin
Sep 1, 2017·The Journal of Cell Biology·Heidi K Norton, Jennifer E Phillips-Cremins
Nov 23, 2017·Nature Communications·Stephan NothjungeRalf Gilsbach
Oct 5, 2017·Nature·Rachel Patton McCord
Oct 27, 2017·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Tatsuya HiranoKatsuhiko Shirahige
Oct 24, 2017·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Francesco N CarelliJulie Ahringer
Apr 28, 2018·Current Opinion in Hematology·Sergi Cuartero, Matthias Merkenschlager
Aug 30, 2017·Journal of Developmental Origins of Health and Disease·E JacobsonJ M O'Sullivan
Oct 19, 2017·Development·Nicola FestucciaPablo Navarro
Dec 16, 2017·Bioinformatics·Xiaobin Zheng, Yixian Zheng
Jun 16, 2018·F1000Research·Anita Göndör, Rolf Ohlsson
Dec 4, 2017·Cold Spring Harbor Symposia on Quantitative Biology·Sarah C Hsu, Gerd A Blobel
May 8, 2018·Cold Spring Harbor Symposia on Quantitative Biology·Geoffrey FudenbergLeonid A Mirny
Apr 25, 2018·Cold Spring Harbor Symposia on Quantitative Biology·Rafael Galupa, Edith Heard
Feb 24, 2018·Cold Spring Harbor Symposia on Quantitative Biology·Qian BianBarbara J Meyer
Jul 11, 2018·ELife·Lindsey E MontefioriMarcelo A Nóbrega
Aug 8, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Katerina Cermakova, H Courtney Hodges
Jul 25, 2018·Journal of Thrombosis and Haemostasis : JTH·C Espitia JaimesM Neerman-Arbez
May 26, 2018·Circulation Research·Manuel Rosa-GarridoThomas M Vondriska
Apr 28, 2018·Circulation Research·Kevin C Wang, Howard Y Chang
Sep 29, 2018·Science·Eileen E M Furlong, Michael Levine
Oct 28, 2018·Nature Reviews. Genetics·M Jordan Rowley, Victor G Corces
Sep 27, 2018·Annual Review of Genetics·Rafael Galupa, Edith Heard
Oct 28, 2017·Nucleus·Victor V Lobanenkov, Gabriel E Zentner
Oct 28, 2017·Nucleus·Anders S HansenRobert Tjian
Dec 21, 2018·Biophysics Reviews·Koustav PalFrancesco Ferrari
Jan 30, 2018·Clinical Genetics·J-F OuimetteR A Veitia

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Cell eTOC

Cell is a scientific journal publishing research across a broad range of disciplines within the life sciences field. Discover the latest research from Cell here.