Holocarboxylase synthetase histone biotinylation

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. 

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. 

Bao, B., Pestinger, V., Hassan, Y.I., Borgstahl, G.E.O., Kolar, C., and Zempleni, J., 2011. Holocarboxylase synthetase is a chromatin protein and interacts directly with histone H3 to mediate biotinylation of K9 and K18. Journal of Nutritional Biochemistry. 22 470-475. 

Bao, B., Rodriguez-Melendez, R., and Zempleni, J., 2012. Cytosine methyla-tion in miR-153 gene promoters increases the expression of holocarboxylase synthetase, thereby increasing the abundance of histone H4 biotinylation marks in HEK-293 human kidney cells. The Journal of Nutritional Biochemistry. 23 635-639. 

Camporeale, G., Giordano, E., Rendina, R., Zempleni, J., and Eissenberg, J.C., 2006. Drosophila holocarboxylase synthetase is a chromosomal protein required for normal histone biotinylation, gene transcription patterns, lifespan and heat tolerance. Journal of Nutrition. 136 2735-2742. 

Narang, M.A., Dumas, R., Ayer, L.M., and Gravel, R.A., 2004. Reduced histone biotinylation in multiple carboxylase deficiency patients a nuclear role for holocarboxylase synthetase. Human Molecular Genetics. 13 15-23. 

Narang MA, Dnmas R, Ayer LM, and Gravel RA. Rednced histone biotinylation in mnltiple carboxylase deficiency patients A nuclear role for holocarboxylase synthetase. Hum. Mol. Genet. 13 15-23 (2004). 

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