Genome-wide survey of D/E repeats in human proteins uncovers their instability and aids in identifying their role in the chromatin regulator ATAD2

Autor: Shalabh Shukla, Pavlo Lazarchuk, Maria N. Pavlova, Julia M. Sidorova
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: iScience, Vol 25, Iss 12, Pp 105464- (2022)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2022.105464
Popis: Summary: D/E repeats are stretches of aspartic and/or glutamic acid residues found in over 150 human proteins. We examined genomic stability of D/E repeats and functional characteristics of D/E repeat-containing proteins vis-à-vis the proteins with poly-Q or poly-A repeats, which are known to undergo pathologic expansions. Mining of tumor sequencing data revealed that D/E repeat-coding regions are similar to those coding poly-Qs and poly-As in increased incidence of trinucleotide insertions/deletions but differ in types and incidence of substitutions. D/E repeat-containing proteins preferentially function in chromatin metabolism and are the more likely to be nuclear and interact with core histones, the longer their repeats are. One of the longest D/E repeats of unknown function is in ATAD2, a bromodomain family ATPase frequently overexpressed in tumors. We demonstrate that D/E repeat deletion in ATAD2 suppresses its binding to nascent and mature chromatin and to the constitutive pericentromeric heterochromatin, where ATAD2 represses satellite transcription.
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