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Updated: Sep 1, 2025
10:06
Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
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Histone Marks-Dependent Effect on Alternative Splicing: New Perspectives for Targeted Splicing Modulation in Cancer?
Carol Imbriano1, Silvia Belluti1
1Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 213/D, 41125 Modena, Italy.
International Journal of Molecular Sciences
|August 12, 2022
Summary
Histone modifications regulate alternative splicing (AS) by influencing chromatin and RNA processing. Dysfunctional epigenetic splicing codes, marked by altered histone modifications, lead to aberrant AS in cancer, with potential for targeted epigenetic modulation.
Area of Science:
- Molecular Biology
- Epigenetics
- Cancer Biology
Background:
- Alternative splicing (AS) generates proteomic diversity from a limited gene set, controlled by RNA motifs and chromatin.
- Histone modifications, beyond nucleosome positioning, fine-tune AS by affecting transcriptional elongation and splicing factor recruitment.
- Aberrant AS in tumors is linked to a dysfunctional epigenetic splicing code, including altered histone modifications.
Purpose of the Study:
- To review the impact of histone modifications and variants on alternative splicing outcomes.
- To elucidate how a faulty epigenetic splicing code drives aberrant AS in cancer.
- To highlight novel programmable DNA-targeting technologies for AS-targeted epigenetic modulation.
Main Methods:
- Literature review of studies on histone modifications, chromatin, and alternative splicing.
- Analysis of mechanisms linking epigenetic dysregulation to aberrant AS in cancer.
- Survey of recent advances in DNA-targeting technologies for epigenetic modulation.
Main Results:
- Histone modifications and chromatin structure play critical roles in regulating alternative splicing.
- Dysfunctional epigenetic splicing codes, characterized by altered histone marks, are implicated in cancer-associated aberrant AS.
- Programmable DNA-targeting technologies offer potential therapeutic strategies for modulating AS in cancer.
Conclusions:
- Histone modifications are integral regulators of alternative splicing.
- Aberrant epigenetic splicing codes contribute significantly to cancer development through misregulated AS.
- Targeted epigenetic modulation holds promise for future cancer therapies.
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