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肿瘤形成评论综述™
SJR: 0.631 SNIP: 0.503 CiteScore™: 2.2

ISSN 打印: 0893-9675
ISSN 在线: 2162-6448

肿瘤形成评论综述™

DOI: 10.1615/CritRevOncog.2014012463
pages 1-17

Deacetylation of Chromatin and Gene Expression Regulation: A New Target for Epigenetic Therapy

Heidi 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 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. La Thangue
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

ABSTRACT

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.


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