Y chromosome-coded HSATII repeats may contribute to higher incidence of cancer in men

Hegyi, H.; Lexa, M.

doi:10.1101/2024.08.16.608341

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bioRxiv · 10.1101/2024.08.16.608341

Y chromosome-coded HSATII repeats may contribute to higher incidence of cancer in men

Hegyi, H.·Lexa, M.

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Abstract

It has been observed that men have a shorter lifespan and higher incidence of certain cancers than women. We postulate here that this phenomenon may be attributed to the "toxic Y chromosome", owing to the expression of normally silent HSATII repeats in cancer, abundantly present on chromosome Y. Investigating the contribution of all repetitive elements to chromatin interactions using a genome-wide HiC set derived from a colon cancer cell line (HCT116), we found several anomalies regarding satellite HSATII elements when compared to other genomic repeat types: (i) HSATII repeats tend to form HiC pairs mostly with their own kind, and depleted in most heterologous repeat pairs, whereas other types of repeats readily form heterologous HiC pairs; (ii) when treated with 5aza, a chemotherapeutic agent, the number of long-distance HSATII-overlapping HiC pairs significantly decreased when compared to the untreated samples; (iii) and most importantly, in the treated samples interchromosomal HiC read pairs involving a chromosome Y-located repeat and an HSATII repeat on either end almost completely disappear. (iv) We also found that HSATII repeats lack overlap with other types of repeats. To account for these anomalies we queried non-B DNA structure forming such as G-quadruplexes and transcription-related triplex forming. We found that Y chromosome-coded HSATII repeats form significantly stronger triplexes than HSATII repeats on other chromosomes, their strength significantly correlating with the number of HiC reads they overlap with. We surmise that the above phenomena may cause the higher incidence of cancer in men and may lead to the disappearance of the Y chromosome observed in cancerous cells in men.

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Hegyi, H., Lexa, M.. 2024-08-19. Y chromosome-coded HSATII repeats may contribute to higher incidence of cancer in men. https://doi.org/10.1101/2024.08.16.608341

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