How do histone deacetylase inhibitors work?
HDACs can act as transcription repressors, due to histone deacetylation, and consequently promote chromatin condensation. HDAC inhibitors (HDACi) selectively alter gene transcription, in part, by chromatin remodeling and by changes in the structure of proteins in transcription factor complexes (Gui et al., 2004).
What do Hypomethylating agents do?
A hypomethylating agent (or demethylating agent) is a drug that inhibits DNA methylation. Because DNA methylation affects cellular function through successive generations of cells without changing the underlying DNA sequence, hypomethylating agents are considered a type of epigenetic therapy.
What is the role of histone deacetylase HDAC inhibitors?
Histone deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation, inducing death, apoptosis, and cell cycle arrest in cancer cells.
How does histone acetylation affect gene expression?
Histone acetylation is a critical epigenetic modification that changes chromatin architecture and regulates gene expression by opening or closing the chromatin structure. It plays an essential role in cell cycle progression and differentiation.
What is the difference between acetylation and methylation?
The main difference between acetylation and methylation is that acetylation introduces an acetyl group to a chemical compound as a functional group whereas methylation introduces a methyl group to a chemical compound.
What are the major mechanisms of epigenetic genome modification?
Cellular
- Epigenetic mechanisms form a layer of control within a cell that regulates gene expression and silencing.
- Three different epigenetic mechanisms have been identified: DNA methylation, histone modification, and non-coding RNA (ncRNA)-associated gene silencing.
What are Hypomethylating agents AML?
Decitabine and guadecitabine are hypomethylating agents (HMAs) that exert inhibitory effects against cancer cells. This includes stimulation of anti-tumor immunity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients.
Is azacitidine a hypomethylating agent?
The hypomethylating agents (HMAs), decitabine and azacitidine, are valuable treatment options in acute myeloid leukemia patients who are not eligible for intensive chemotherapy. Both agents are generally well tolerated, and complications most commonly relate to myelosuppression.
Why does histone methylation occur over large areas of chromatin?
Due to its ability to either activate or repress the recruitment of regulatory proteins to the chromatin, histone methylation plays an integral role in regulating DNA transcription in the cell.
What are the two general mechanisms by which histone acetylation affects transcription?
Acetylation removes positive charges thereby reducing the affinity between histones and DNA. Thus, in most cases, histone acetylation enhances transcription while histone deacetylation represses transcription, but the reverse is seen as well (Reamon-Buettner and Borlak, 2007).