Histone-acetylating enzyme of brain

Area of Science:

• Biochemistry
• Molecular Biology
• Neuroscience

Background:

• Histone acetylation is a key epigenetic mechanism regulating gene expression.
• Histone acetylase enzymes play a critical role in modifying chromatin structure.
• Understanding the tissue-specific activity of histone acetylase is important for elucidating its role in cellular function.

Purpose of the Study:

• To investigate the properties and activity of histone acetylase in rat brain and liver.
• To determine the subcellular localization and substrate specificity of histone acetylase.
• To compare histone acetylase activity between developing and adult rats, and between brain and liver tissues.

Main Methods:

• Enzyme assays using [1-(14)C]acetyl-CoA as the acetyl donor.
• Isolation and purification of nuclear fractions via sucrose density gradient centrifugation.
• Partial purification of the enzyme using ammonium sulfate fractionation.
• Assays with different histone fractions and other proteins (polylysine, protamine, albumin, globulin).

Main Results:

• Histone acetylase activity was predominantly localized to the nucleus in both brain and liver.
• Cerebral nuclei from adult rats showed higher histone acetylase activity compared to newborn rats.
• Adult rat brain exhibited greater nuclear acetylating activity than liver.
• The partially purified enzyme specifically acetylated histones, with a preference for arginine-rich (F3) and slightly lysine-rich (F2a, F2b) fractions over lysine-rich (F1) fractions.
• Acetylation of chromatin-bound proteins was less extensive than that of free histones.

Conclusions:

• Histone acetylase activity is primarily nuclear and exhibits developmental and tissue-specific differences.
• The enzyme preferentially acetylates specific histone fractions, suggesting a role in regulating gene expression.
• The high activity in the mature brain suggests a significant role for histone acetylation in the genetic control of cerebral function.