Deacetylation of chromatin and gene expression regulation: a new target for epigenetic therapy.
Besides the genetic information thath is encoded by DNA, heritable information can also be passed on without relying on changes in the nucleotide sequence of DNA, a phenomenon known as epigenetics. Gene expression in eukaryotes is partly regulated by epigenetic mechanisms both at the DNA and histone protein levels. Chromatin structure can be influenced by various modifications, including the reversible posttranslational processes of acetylation and deacetylation of DNA-binding proteins. Histone acetyl transferase (HAT) is referred to as the writer of this process, whereas histone deacetylase (HDAC) is the eraser of this lysine modification. Dysregulation of gene expression and changes in the HDAC expression profile have been associated with carcinogenesis, and HDAC inhibitors are already approved for the treatment of cutaneous T-cell lymphoma and peripheral T-cell lymphoma. These inhibitors are able to influence epigenetic processes by targeting HDAC activity, increasing nuclear histone acetylation status, and contributing to chromatin remodeling, thereby affecting gene expression. In addition, HDACs also act on a plethora of cytosolic proteins with many cellular functions, including angiogenesis, immune responses, and autophagy. In this review, we will give an overview of histone deacetylase and how it can regulate gene expression at the chromatin level.
Laboratory of Cancer Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Old Road Campus, off Roosevelt Drive, Oxford, OX3 7DQ, UK.
Heidi
H
Olzscha
Laboratory of Cancer Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Old Road Campus, off Roosevelt Drive, Oxford, OX3 7DQ, UK.
Semira
S
Sheikh
Laboratory of Cancer Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Old Road Campus, off Roosevelt Drive, Oxford, OX3 7DQ, UK.
Nicholas B
NB
La Thangue
D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000502:physiology*; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000639:trends; D009369:Neoplasms / Q000235:genetics / Q000628:therapy
D002843:Chromatin; D006657:Histones; D007527:Isoenzymes; D006655:Histone Deacetylases