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Genome-wide screening and functional validation of methylation barriers near promoters
Shu, Jingmin Jelinek, Jaroslav Chen, Hai Zhang, Yan Qin, Taichun Li, Ming Liu, Li Issa, Jean-Pierre J.
Shu, Jingmin
Jelinek, Jaroslav
Chen, Hai
Zhang, Yan
Qin, Taichun
Li, Ming
Liu, Li
Issa, Jean-Pierre J.
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2024-04-22
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https://doi.org/10.1093/nar/gkae302
Abstract
CpG islands near promoters are normally unmethylated despite being surrounded by densely methylated regions. Aberrant hypermethylation of these CpG islands has been associated with the development of various human diseases. Although local genetic elements have been speculated to play a role in protecting promoters from methylation, only a limited number of methylation barriers have been identified. In this study, we conducted an integrated computational and experimental investigation of colorectal cancer methylomes. Our study revealed 610 genes with disrupted methylation barriers. Genomic sequences of these barriers shared a common 41-bp sequence motif (MB-41) that displayed homology to the chicken HS4 methylation barrier. Using the CDKN2A (P16) tumor suppressor gene promoter, we validated the protective function of MB-41 and showed that loss of such protection led to aberrant hypermethylation. Our findings highlight a novel sequence signature of cis-acting methylation barriers in the human genome that safeguard promoters from silencing.
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Jingmin Shu, Jaroslav Jelinek, Hai Chen, Yan Zhang, Taichun Qin, Ming Li, Li Liu, Jean-Pierre J Issa, Genome-wide screening and functional validation of methylation barriers near promoters, Nucleic Acids Research, Volume 52, Issue 9, 22 May 2024, Pages 4857–4871, https://doi.org/10.1093/nar/gkae302
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Oxford University Press (OUP)
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Nucleic Acids Research, Vol. 52, Iss. 9
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Attribution-NonCommercial CC BY-NC