Chromatin remodeling in replication-uncoupled maintenance DNA methylation and chromosome stability: Insights from ICF syndrome studies.

研究成果: Contribution to journalReview article査読

抄録

Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is characterized by frequent appearance of multiradial chromosomes, which are distinctive chromosome fusions that occur at hypomethylated pericentromeric regions comprising repetitive sequences, in activated lymphocytes. The syndrome is caused by mutations in DNMT3B, ZBTB24, CDCA7, or HELLS. De novo DNA methylation is likely defective in patients with ICF syndrome harboring mutations in DNMT3B, whereas accumulating evidence suggests that replication-uncoupled maintenance DNA methylation of late-replicating regions is impaired in patients with ICF syndrome harboring mutations in ZBTB24, CDCA7, or HELLS. ZBTB24 is a transcriptional activator of CDCA7, and CDCA7 and HELLS compose a chromatin remodeling complex and are involved in the maintenance DNA methylation through an interaction with UHRF1 in a feed-forward manner. Furthermore, our recent studies possibly provided the missing link between DNA hypomethylation and the formation of the abnormal chromosomes; it could occur via aberrant transcription from the hypomethylated regions, followed by pathological R-loop formation. The homologous-recombination dominant condition caused by a defect in non-homologous end joining observed in several types of ICF syndrome could facilitate the formation of multiradial chromosomes. Here, the latest knowledge regarding maintenance DNA methylation and chromosome stability provided by those studies is reviewed.
本文言語英語
ページ(範囲)349-359
ジャーナルGenes to Cells
26
6
DOI
出版ステータス出版済み - 6 7 2021

フィンガープリント

「Chromatin remodeling in replication-uncoupled maintenance DNA methylation and chromosome stability: Insights from ICF syndrome studies.」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル