The role of holocarboxylase synthetase in genome stability is mediated partly by epigenomic synergies between methylation and biotinylation events

Zempleni, Janos; Li, Yong; Xue, Jing; Cordonier, Elizabeth L.

doi:10.4161/epi.6.7.15544

Cited by 8 publications

(3 citation statements)

References 42 publications

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“…However, this biotinylation activity of HCS in vitro is consistent with promiscuous biotin transfer from the biotinyl-AMP product of the HCS reaction to nearby protein lysines, as described by Healy et al (38). Further, efforts to detect biotinylated EHMT1 in HEK-293 cells have failed (107). A role for biotin in the in vivo function of nuclear HCS remains elusive.…”

Section: Nuclear Hcs: a Biotin-independent Transcriptional Corepressorsupporting

confidence: 78%

Holocarboxylase Synthetase: A Moonlighting Transcriptional Coregulator of Gene Expression and a Cytosolic Regulator of Biotin Utilization

2017

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The vitamin biotin is an essential nutrient for the metabolism and survival of all organisms owing to its function as a cofactor of enzymes collectively known as biotin-dependent carboxylases. These enzymes use covalently attached biotin as a vector to transfer a carboxyl group between donor and acceptor molecules during carboxylation reactions. In human cells, biotin-dependent carboxylases catalyze key reactions in gluconeogenesis, fatty acid synthesis, and amino acid catabolism. Biotin is attached to apocarboxylases by a biotin ligase: holocarboxylase synthetase (HCS) in mammalian cells and BirA in microbes. Despite their evolutionary distance, these proteins share structural and sequence similarities, underscoring their importance across all life forms. However, beyond its role in metabolism, HCS participates in the regulation of biotin utilization and acts as a nuclear transcriptional coregulator of gene expression. In this review, we discuss the function of HCS and biotin in metabolism and human disease, a putative role for the enzyme in histone biotinylation, and its participation as a nuclear factor in chromatin dynamics. We suggest that HCS be classified as a moonlighting protein, with two biotin-dependent cytosolic metabolic roles and a distinct biotin-independent nuclear coregulatory function.

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Section: Nuclear Hcs: a Biotin-independent Transcriptional Corepressorsupporting

confidence: 78%

Holocarboxylase Synthetase: A Moonlighting Transcriptional Coregulator of Gene Expression and a Cytosolic Regulator of Biotin Utilization

2017

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“…Other disorders are often associated with B 7 deficiency (e.g., dermatitis, conjunctivitis, ataxia, neurological disorders, developmental delay), but no underlying biochemical cause has been described (Wolf 2005;Suzuki et al 2005;Rébeillé et al 2007). Biotinylation depends on prior DNA methylation (Zempleni et al 2011), creating epigenetic synergies between biotinylation and methylation events that might offer an explanation to these disorders (Zempleni et al 2012). Furthermore, there is a correlation between human tumors and alterations in biotin cycling, probably associated with histone biotinylation impairment (Zempleni et al 2011).…”

Section: Functions Of Plant Amino Acid-based Vitamins In Humansmentioning

confidence: 98%

“…Biotinylation depends on prior DNA methylation (Zempleni et al 2011), creating epigenetic synergies between biotinylation and methylation events that might offer an explanation to these disorders (Zempleni et al 2012). Furthermore, there is a correlation between human tumors and alterations in biotin cycling, probably associated with histone biotinylation impairment (Zempleni et al 2011).…”

Section: Functions Of Plant Amino Acid-based Vitamins In Humansmentioning

confidence: 98%

Plant amino acid-derived vitamins: biosynthesis and function

Miret

Munné‐Bosch

2013

Amino Acids

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Vitamins are essential organic compounds for humans, having lost the ability to de novo synthesize them. Hence, they represent dietary requirements, which are covered by plants as the main dietary source of most vitamins (through food or livestock's feed). Most vitamins synthesized by plants present amino acids as precursors (B1, B2, B3, B5, B7, B9 and E) and are therefore linked to plant nitrogen metabolism. Amino acids play different roles in their biosynthesis and metabolism, either incorporated into the backbone of the vitamin or as amino, sulfur or one-carbon group donors. There is a high natural variation in vitamin contents in crops and its exploitation through breeding, metabolic engineering and agronomic practices can enhance their nutritional quality. While the underlying biochemical roles of vitamins as cosubstrates or cofactors are usually common for most eukaryotes, the impact of vitamins B and E in metabolism and physiology can be quite different on plants and animals. Here, we first aim at giving an overview of the biosynthesis of amino acid-derived vitamins in plants, with a particular focus on how this knowledge can be exploited to increase vitamin contents in crops. Second, we will focus on the functions of these vitamins in both plants and animals (and humans in particular), to unravel common and specific roles for vitamins in evolutionary distant organisms, in which these amino acid-derived vitamins play, however, an essential role.

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