Histone acetylation in chromatin structure and transcription

Abstract

'The amino termini of histones extend from the nucleosomal core and are modified by acetyltransferases and deacetylases during the cell cycle. These acetylation patterns may direct histone assembly and help regulate the unfolding and activity of genes.

Chemistry, Biology, and QSAR Studies of Substituted Biaryl Hydroxamates and Mercaptoacetamides as HDAC Inhibitors—Nanomolar‐Potency Inhibitors of Pancreatic Cancer Cell Growth

“…The crude material was purified by flash chromatography (acetone/hexane, 1:1) to give compound 3d (1.6 g, 58%). 1 A suspension of compound 3d (1.80 g, 3.5 mmol) and Pd(OH) 2 /C (20 wt. %, 0.5 g) in a mixture of methanol (10 mL) and CH 2 Cl 2 (10 mL) was stirred under hydrogen atmosphere for 4h at room temperature.…”

“…The catalyst was removed by filtration through a pad of Celite and the solvent was evaporated to give a residue which was purified by flash chromatography (ethyl acetate/hexane 1:1 then 2:1) to give compound 4d (1.40 g, 83%). 1 To a stirred solution of 7-benzyloxycarbamoylheptanoic acid (5) (0.13 g, 0.46 mmol) in dry DMF (5 mL) DIPEA (0.120 g, 0.92 mmol) was added, and the mixture was stirred for 10 min at room temperature. Then PyBOP (0.480 g, 0.92 mmol) and biphenyl amine 4d (0.220 g, 0.46 mmol) were added sequentially and stirring was continued over night.…”

“…A shift in the balance of acetylation on chromatin may result in changes in the regulation of patterns of gene expression. [1][2][3][4] Since many cancers are associated with aberrant transcriptional activity, and the HDACs can affect transcription factors and gene regulation, these enzymes have been identified as attractive targets for cancer therapy. Indeed, chemical inhibitors of HDACs have been shown to inhibit tumor cell growth and induce differentiation and cell death.…”

The adenovirus E1A binding protein BS69 is a corepressor of transcription through recruitment of N-CoR

“…Acetylation of N-terminal tails of histones weakens the interaction of histones with DNA and facilitates remodelling of the nucleosome structure into a more open conformation to allow access of transcription factors and the basal transcription machinery (Grunstein, 1997). Deacetylation of histone N-terminal tails can reverse this process and hypoacetylated regions of chromatin are transcriptionally less accessible.…”

Epigenetic regulation of protein tyrosine phosphatases: potential molecular targets for cancer therapy

“…42 Transcriptionally active chromatin is usually associated with hyperacetylated histones, while transcriptionally inactive heterochromatin is associated with hypoacetylated histones. 60 Unlike histone acetylation, histone methylation can either activate (K4 of histone H3) or repress (K9 of H3) gene transcription. 61 Genetic evidence suggests a link between histone modification and DNA methylation, which has prompted epigenetic targeting to reexpress genes by increasing histone acetyl transferase enzyme activity and/or inhibiting histone deacetylase (HDAC) enzymes.…”