Cryptic transcription in aging.
Abstract
Cryptic transcription is an aberrant form of transcription that initiates from non-canonical, non-promoter regions within the gene. In mammals, a repressive chromatin state effectively inhibits cryptic transcription, preserving transcriptional fidelity. Aging-induced loss of trimethylated lysine 36 on histone H3 reduces DNA methylation, and accumulation of promoter-like histone modifications renders gene bodies permissive to spurious initiation by RNA polymerase II. This allows previously repressed intragenic regions to acquire promoter-like chromatin features. Cryptic transcription produces aberrant RNAs that interfere with normal gene expression, leading to truncated proteins or nonfunctional mRNAs. The aberrant RNA and protein products impair stem cell self-renewal and differentiation, thereby contributing to the development of aging and disease. This review summarizes the mechanisms underlying age-related cryptic transcription, focusing on the function of H3K36me3, DNA methylation, H3K4me3, H3K27ac, and transcription factors. In addition, we discuss the effects of cryptic transcription on aging stem cells and aged tissues.
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Research summary
The paper proposes that age-related loss of H3K36me3 and subsequent DNA methylation changes lead to cryptic transcription, which impairs stem cell function and contributes to aging. This is a relevant mechanistic review linking epigenetic maintenance to cellular aging, but as a review summarizing known associations rather than presenting novel experimental data or a transformative intervention, its impact is limited to incremental understanding of aging mechanisms.
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