Histones biotinylation

Biotin is also covalently attached to histones, but the abundance of biotinylated histones is low. It is unclear whether the eifects of histone biotinylation in gene repression and genome stability are mediated by histone biotinylation or by interactions of holocarboxylase synthetase with other chromatin proteins. 

Camporeale, G., Oommen, A.M., Griffin, J.B., Sarath, G., and Zempleni, J., 2007. K12-biotinylated histone H4 marks heterochromatin in human lymphoblastoma cells. The Journal of Nutritional Biochemistry. 18 760-768. 

K12-biotinylated histone H4 marks heterochromatin in human lymphoblastoma cells. /. Nutr. Biochem., 18, 760-768. 

RIOS-AVILA, L., PESTINGER, V, WIJERATNE, S. S. K., ZEMPLENL J. (2012) K16-biotinylated histone H4 is overrepresented in repeat regions and participates in the repression of transcriptionally competent genes in human Jurkat lymphoid cells. /. Nutr. Biochem., 23, 1559-1564. 

In 1995, Hymes and Wolf discovered that biotini-dase can act as a biotinyl-transferase biocytin serves as the source of biotin, and histones are specifically biotinylated. Approximately 25% of total cellular biotinidase activity occurs in the nucleus. Zempleni and coworkers demonstrated that the abundance of biotinylated histones varies with the cell cycle, that biotinylated histones are increased approximately twofold compared to quiescent lymphocytes, and that histones are debiotinylated enzymatically in a process that is at least partially catalyzed by biotinidase. These observations suggest that biotin plays a role in regulating DNA transcription and regulation. 

Nare, B., Allocco, J.J., Kuningas, R., Galuska, S., Myers, R.W., Bednarek, M.A. and Schmatz, D.M. (1999) Development of a scintillation proximity assay for histone deacetylase using a biotinylated peptide derived from histone-H4. Analytical Biochemistry, 267, 390-396. 

In addition to its hydrolase activity with maximal velocity at acidic pH, biotinidase also possesses biotinyl-transferase activity at physiological pH, resulting in the biotinylation of nucleophilic compounds such as histones [13]. This activity may play an important role in the regulation of gene expression [30]. Both hydrolase and transferase activities are affected in patients with biotinidase deficiency [13]. 

Hymes J, Fleischhauer K, Wolf (1995) Biotinylation of histones by human serum biotinidase assessment of biotinyl-transferase activity in sera from normal individuals and children with biotinidase deficiency. Biochem Mol Med 56 76-83... 

MetabolicaUy, biotin is of central importance in lipogenesis, gluconeogen-esis, and the catabolism of branched-chain (and other) amino acids. There are two well-characterized biotin-responsive inborn errors of metabolism, which are fatal if untreated holocarboxylase synthetase deficiency and biotinidase deficiency. In addition, biotin induces a number of enzymes, including glu-cokinase and other key enzymes of glycolysis. Biotinylation of histones may be important in regulation of the cell cycle. 

Stanley JS, Griffin JB, and Zempleni J (2001) Biotinylation of histones in human cells. Effects of cell proliferation. European Journal of Biochemistry 268, 5424-9. 

All four carboxylases use bicarbonate as their one-carbon substrate and, in all, the biotin is covalently linked by an amide bond between the carboxyl of biotin and an epsilon amino group of a lysyl residue in the holocarboxylase synthase (= biotin ligase) that catalyzes the formation of the covalent bond. Biotinylation of histones is involved in regulation of gene transcription and may also play a role in packaging of deoxyribonucleic acid (DNA). Biotin has also been found to inhibit the generation of reactive oxygen species (ROS) by neutrophils in vitro. 

Figure 5.3 Selected post-translational modifications of human histones. Methylation, acetylation, phosphorylation, biotinylation and ubiquitylation sites have been identified on all four core histones. The modifications shown here should not be regarded as a complete or final list.

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