Epigenetic control of chromosome-associated lncRNA genes essential for replication and stability

Michael B. Heskett, Athanasios E. Vouzas, Leslie G. Smith, Phillip A. Yates, Christopher Boniface, Eric E. Bouhassira, Paul T. Spellman, David M. Gilbert and Mathew J. Thayer ()
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Michael B. Heskett: Stanford University School of Medicine
Athanasios E. Vouzas: Florida State University
Leslie G. Smith: Department of Chemical Physiology and Biochemistry Oregon Health & Science University
Phillip A. Yates: Department of Chemical Physiology and Biochemistry Oregon Health & Science University
Christopher Boniface: Cancer Early Detection Advanced Research Center, Knight Cancer Institute Oregon Health & Science University
Eric E. Bouhassira: Albert Einstein College of Medicine
Paul T. Spellman: Department of Molecular and Medical Genetics Oregon Health & Science University
David M. Gilbert: San Diego Biomedical Research Institute
Mathew J. Thayer: Department of Chemical Physiology and Biochemistry Oregon Health & Science University

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract ASARs are long noncoding RNA genes that control replication timing of entire human chromosomes in cis. The three known ASAR genes are located on human chromosomes 6 and 15, and are essential for chromosome integrity. To identify ASARs on all human chromosomes we utilize a set of distinctive ASAR characteristics that allow for the identification of hundreds of autosomal loci with epigenetically controlled, allele-restricted behavior in expression and replication timing of coding and noncoding genes, and is distinct from genomic imprinting. Disruption of noncoding RNA genes at five of five tested loci result in chromosome-wide delayed replication and chromosomal instability, validating their ASAR activity. In addition to the three known essential cis-acting chromosomal loci, origins, centromeres, and telomeres, we propose that all mammalian chromosomes also contain “Inactivation/Stability Centers” that display allele-restricted epigenetic regulation of protein coding and noncoding ASAR genes that are essential for replication and stability of each chromosome.

Date: 2022
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DOI: 10.1038/s41467-022-34099-7

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