Expression, tandem repeat copy number variation and stability of four macrosatellite arrays in the human genome

Abstract

BackgroundMacrosatellites are some of the largest variable number tandem repeats in the human genome, but what role these unusual sequences perform is unknown. Their importance to human health is clearly demonstrated by the 4q35 macrosatellite D4Z4 that is associated with the onset of the muscle degenerative disease facioscapulohumeral muscular dystrophy. Nevertheless, many other macrosatellite arrays in the human genome remain poorly characterized.ResultsHere we describe the organization, tandem repeat copy number variation, transmission stability and expression of four macrosatellite arrays in the human genome: the TAF11-Like array located on chromosomes 5p15.1, the SST1 arrays on 4q28.3 and 19q13.12, the PRR20 array located on chromosome 13q21.1, and the ZAV array at 9q32. All are polymorphic macrosatellite arrays that at least for TAF11-Like and SST1 show evidence of meiotic instability. With the exception of the SST1 array that is ubiquitously expressed, all are expressed at high levels in the testis and to a lesser extent in the brain.ConclusionsOur results extend the number of characterized macrosatellite arrays in the human genome and provide the foundation for formulation of hypotheses to begin assessing their functional role in the human genome.

Characterization of the ICCE Repeat in Mammals Reveals an Evolutionary Relationship with the DXZ4 Macrosatellite through Conserved CTCF Binding Motifs

“…1 D ), which likely reflects repeat unit copy number variation typical of large tandem repeats (Tremblay et al. 2010; Schaap et al.…”

Epigenetic regulation of the X-chromosomal macrosatellite repeat encoding for the cancer/testis gene CT47

“…A recent publication shows that indeed the family of MSRs exclusively expressed in the germ line and testis is expanding and includes new members like TAF11-Like, PRR20 and ZAV. 9 Understanding the epigenetic organization of MSRs in health and disease, which cover a high portion of the human genome, may therefore significantly advance our understanding of the epigenetic map of the human genome and of germline biology.…”

“…1,5 Other MSRs that have been studied in various details include DXZ4 on the X chromosome, which was recently proposed to have a role in X-chromosome inactivation; 3 RS447, which encodes for a deubiquitinating enzyme; 6 and RNU2, encoding a small nuclear RNA, 7 TAF11-Like, 8,9 which was recently suggested to be involved in a psychiatric disorder, and very recently SST1, PRR20 and ZAV. 9 D4Z4 is characterized by bidirectional transcriptional activity, high DNA methylation and the presence of both heterochromatic histone modifications such as histone 3 lysine 9 trimethylation (H3K9me3) as well as the transcriptionally permissive histone modification such as dimethylated lysine 4 of histone H3 (H3K4me2). Upon contraction, as seen in FSHD, D4Z4 becomes hypomethylated, 10 shows selective loss of H3K9me3, with secondary losses of heterochromatin protein 1g and the cohesin complex, 11 thus leading to a more open chromatin structure.…”

Dysregulation of Long Non-coding RNAs in Human Disease

“…These arrays were once considered to be ''junk'' sequences, but there is increasing evidence for their involvement in gene regulation. Some polymorphic macrosatellites residing within common fragile sites, such as the TAF11-Like array and SST1 arrays, show evidence of meiotic instability and may be associated with diseases (Tremblay et al 2010). In addition, many genomic repeats are subject to PcG-mediated silencing (Leeb et al 2010).…”