Human Satellite 1A analysis provides evidence of pericentromeric transcription

Abstract

Background Pericentromeric regions of human chromosomes are composed of tandem-repeated and highly organized sequences named satellite DNAs. Human classical satellite DNAs are classified into three families named HSat1, HSat2, and HSat3, which have historically posed a challenge for the assembly of the human reference genome where they are misrepresented due to their repetitive nature. Although being known for a long time as the most AT-rich fraction of the human genome, classical satellite HSat1A has been disregarded in genomic and transcriptional studies, falling behind other human satellites in terms of functional knowledge. Here, we aim to characterize and provide an understanding on the biological relevance of HSat1A. Results The path followed herein trails with HSat1A isolation and cloning, followed by in silico analysis. Monomer copy number and expression data was obtained in a wide variety of human cell lines, with greatly varying profiles in tumoral/non-tumoral samples. HSat1A was mapped in human chromosomes and applied in in situ transcriptional assays. Additionally, it was possible to observe the nuclear organization of HSat1A transcripts and further characterize them by 3′ RACE-Seq. Size-varying polyadenylated HSat1A transcripts were detected, which possibly accounts for the intricate regulation of alternative polyadenylation. Conclusion As far as we know, this work pioneers HSat1A transcription studies. With the emergence of new human genome assemblies, acrocentric pericentromeres are becoming relevant characters in disease and other biological contexts. HSat1A sequences and associated noncoding RNAs will most certainly prove significant in the future of HSat research.

Satellite DNAs—From Localized to Highly Dispersed Genome Components

“…Misregulation of satDNA expression can lead to various abnormalities in the genomic architecture, chromosome segregation and gametogenesis. Changes in copy number of satDNAs and their transcription rates may be associated with stress, environmental adaptations and pathological states, such as oncogenic transformation [ 18 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ].…”

Satellite RNAs: emerging players in subnuclear architecture and gene regulation

“…The copy numbers of HSat1 DNA monomers in the genome are also highly variable, but little correlation between genomic copy numbers and RNA expression levels has been detected. Physical mapping of HSat1 lncRNA in the human chromosomes by FISH revealed clear FISH signals in all acrocentric chromosomes and chromosomes 1 and 3 (Lopes et al , 2023 ). RNA‐FISH showed that HSat1A transcripts exhibit cluster‐like organization in the nucleus, albeit with distinct signal patterns in different cell lines.…”

“…A summary of features and functions of satellite RNAs.There had long been a lack of studies on the transcripts from HSat1 regions, but recentlyLopes et al (2023) extensively characterized the expression and intracellular localization of transcripts from HSat1A regions, which are located mostly on chr3, chr4, and chr13. HSat1 expression levels vary markedly in various cancer cell lines and human tissues.…”

Overexpression of Pericentromeric HSAT2 DNA Increases Expression of EMT Markers in Human Epithelial Cancer Cell Lines

“…Despite the initial ideas about transcriptionally silent pericentromeres, we know now that the DNA of all HSAT families (HSAT1-3) can be transcribed in a cell under certain circumstances (stress, malignization, cancer-associated polarization, differentiation, senescence, oogenesis, and embryogenesis) [ 19 , 25 , 41 , 42 , 43 ]. In cancer cells, HSAT DNA and RNA contribute to genetic instability [ 20 , 44 , 45 , 46 , 47 ].…”