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Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture.

Title: Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture.
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Name(s): Darrow, Emily M, author
Huntley, Miriam H, author
Dudchenko, Olga, author
Stamenova, Elena K, author
Durand, Neva C, author
Sun, Zhuo, author
Huang, Su-Chen, author
Sanborn, Adrian L, author
Machol, Ido, author
Shamim, Muhammad, author
Seberg, Andrew P, author
Lander, Eric S, author
Chadwick, Brian P, author
Aiden, Erez Lieberman, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2016-08-02
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the "Barr body." Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called "superdomains," such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called "superloops." DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4 We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging.
Identifier: FSU_pmch_27432957 (IID), 10.1073/pnas.1609643113 (DOI), PMC4978254 (PMCID), 27432957 (RID), 27432957 (EID), 1609643113 (PII)
Keywords: CTCF, Hi‐C, X chromosome inactivation, Genome engineering, Inactive X chromosome
Grant Number: U01 HL130010, U54 HG003067, DP2 OD008540, P50 HG006193, R01 GM073120, RM1 HG006193
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978254.
Subject(s): Animals
Binding Sites/genetics
CCCTC-Binding Factor/metabolism
Chromatin/genetics
Chromatin/metabolism
Chromosome Mapping
Chromosomes, Human, X/genetics
Female
Gene Deletion
Genome, Human/genetics
Humans
Macaca mulatta
Mice
Microsatellite Repeats/genetics
Protein Binding
X Chromosome Inactivation
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_27432957
Host Institution: FSU
Is Part Of: Proceedings of the National Academy of Sciences of the United States of America.
1091-6490
Issue: iss. 31, vol. 113

Choose the citation style.
Darrow, E. M., Huntley, M. H., Dudchenko, O., Stamenova, E. K., Durand, N. C., Sun, Z., … Aiden, E. L. (2016). Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture. Proceedings Of The National Academy Of Sciences Of The United States Of America. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_27432957