Acetylated histone H3 refers to histone H3 proteins that carry acetyl groups, typically on lysine residues, which leads to a more relaxed chromatin structure and generally correlates with active gene transcription.
– Levels of Ac-histone H3 can serve as a biomarker reflecting the balance between histone acetyltransferase (HAT) activity and HDAC activity in the cell.
• Role in Cancer:
– Altered acetylation levels may contribute to dysregulated gene expression in cancer cells.
– Low levels of histone acetylation (including Ac-histone H3) are often associated with the silencing of tumor suppressor genes, whereas increased acetylation after treatment with HDAC inhibitors is correlated with reactivation of key regulatory pathways.
– The acetylation state of histone H3 can be used as an indicator of treatment response, and higher acetylation levels after HDAC inhibition often correlate with favorable treatment outcomes.
• Therapeutic and Immunotherapy Implications:
– HDAC inhibitors aim to increase acetylated histone levels (including Ac-histone H3), thereby promoting a more open chromatin conformation that facilitates transcription of genes involved in differentiation, apoptosis, and immune recognition.
– Increased acetylation can enhance the expression of cancer antigens and immune modulatory molecules, potentially sensitizing tumor cells to immune-mediated attack.
– Combination therapies that include HDAC inhibitors and immunotherapeutic agents (such as checkpoint inhibitors) are being actively investigated to enhance antitumor responses by both directly affecting cancer cell survival pathways and by modulating the tumor microenvironment.
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