Histone acetylation and disease

Abstract

Differential acetylation of histones and transcription factors plays an important regulatory role in developmental processes, proliferation and differentiation. Aberrant acetylation or deacetylation leads to such diverse disorders as leukemia, epithelial cancers, fragile X syndrome and Rubinstein-Taybi syndrome. The various groups of histone acetyltransferases (CBP/p300, GNAT, MYST, nuclear receptor coactivators and TAFII250) and histone deacetylases are surveyed with regard to their possible or known involvement in cancer progression and human developmental disorders. Current treatment strategies are discussed, which are still mostly limited to histone deacetylase inhibitors such as trichostatin A and butyrate.

Acetylation regulates DNA repair mechanisms in human cells

“…[1][2][3] The importance of this protein modification is emphasized by the fact that some cancers are associated with deregulated acetylation of lysine residues in histones, transcription factors or in critical regulatory proteins, such as tumor suppressor p53 or proto-oncogene Ras. [4][5][6][7] Whereas the influence of acetylation on the structure of chromatin has been well defined, recent studies indicate that acetylation also regulates activity of DNA repair proteins. The link between acetylation and DNA damage repair was first detected in mammalian cells with induced hyperacetylation after exposure to a deacetylase inhibitor.…”

High-resolution mapping of H4K16 and H3K23 acetylation reveals conserved and unique distribution patterns inArabidopsisand rice

“…[4][5][6][7] Histone acetylation homeostasis plays a vital role in a diverse array of biological processes, including DNA replication, DNA repair, gene silencing, genome defense, genome organization, normal growth and development, physiology, aging, and numerous diseases. [8][9][10][11][12][13] In plants, recent advances in high throughput sequencing technology have enabled the large-scale profiling of histone acetylation marks and have greatly improved our understanding of the function of histone acetylation and its relationship with transcription. [14][15][16][17][18] Besides its role in gene expression, plant histone acetylation plays crucial roles in the crosstalk between genomes and the environment during plant responses to diverse stresses at the cellular and organismal levels.…”

Chemistry of acetyl transfer by histone modifying enzymes: structure, mechanism and implications for effector design

“…Considering the important role that HATs and HDACs play in gene regulation, it has not come as a surprise that alterations in HAT and HDAC activity have been correlated with human diseases. For example, chromosomal translocations involving the monocytic leukemia zinc finger protein (MOZ) and p300/CBP HATs are associated with acute myeloid leukemias and p300/CBP have properties of tumor suppressor proteins (Muraoka et al, 1996;Giles et al, 1998;Chaffanet et al, 2000;Timmermann, 2001). In addition, class I/II HDACs have emerged as attractive targets for cancer therapy, as HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies (Kelly et al, 2002(Kelly et al, , 2003Marks and Jiang, 2005;Bolden et al, 2006).…”