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Cobalamin's (Vitamin B12) Surprising Function as a Photoreceptor.

ABSTRACT: Cobalamin (Vitamin B12) is an adenosyl- or methyl-donating cofactor for many enzymes, yet many proteins with unknown or nonenzymatic function also contain B12-binding domains. Recent studies show that light excitation energy can promote covalent linkage of B12 to transcription factors with this linkage, affecting gene expression. Thus, B12 now has a newly described regulatory function. Here, our bioinformatics analysis reveals other transcription factors, photoreceptors, kinases, and oxygen sensors that harbor a B12-binding domain that could also regulate activity in response to light absorption.

SUBMITTER: Cheng Z

PROVIDER: S-EPMC4967030 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Cobalamin's (Vitamin B12) Surprising Function as a Photoreceptor.

Cheng Zhuo Z Yamamoto Haruki H Bauer Carl E CE

Trends in biochemical sciences 20160521 8

Cobalamin (Vitamin B12) is an adenosyl- or methyl-donating cofactor for many enzymes, yet many proteins with unknown or nonenzymatic function also contain B12-binding domains. Recent studies show that light excitation energy can promote covalent linkage of B12 to transcription factors with this linkage, affecting gene expression. Thus, B12 now has a newly described regulatory function. Here, our bioinformatics analysis reveals other transcription factors, photoreceptors, kinases, and oxygen sens ...[more]

PMID: 27217104

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Project description:Purple nonsulfur bacteria adapt their physiology to a wide variety of environmental conditions often through the control of transcription. One of the main transcription factors involved in controlling expression of the Rhodobacter capsulatus photosystem is CrtJ, which functions as an aerobic repressor of photosystem genes. Recently, we reported that a vitamin B12 binding antirepressor of CrtJ called AerR is required for anaerobic expression of the photosystem. However, the mechanism whereby AerR regulates CrtJ activity is unclear. In this study, we used a combination of next-generation sequencing and biochemical methods to globally identify genes under control of CrtJ and the role of AerR in controlling this regulation. Our results indicate that CrtJ has a much larger regulon than previously known, with a surprising regulatory function under both aerobic and anaerobic photosynthetic growth conditions. A combination of in vivo chromatin immunoprecipitation-DNA sequencing (ChIP-seq) and ChIP-seq and exonuclease digestion (ChIP-exo) studies and in vitro biochemical studies demonstrate that AerR forms a 1:2 complex with CrtJ (AerR-CrtJ2) and that this complex binds to many promoters under photosynthetic conditions. The results of in vitro and in vivo DNA binding studies indicate that AerR-CrtJ2 anaerobically forms an extended interaction with the bacteriochlorophyll bchC promoter to relieve repression by CrtJ. This is contrasted by aerobic growth conditions where CrtJ alone functions as an aerobic repressor of bchC expression. These results indicate that the DNA binding activity of CrtJ is modified by interacting with AerR in a redox-regulated manner and that this interaction alters CrtJ's function.IMPORTANCE Photoreceptors control a wide range of physiology often by regulating downstream gene expression in response to light absorption via a bound chromophore. Different photoreceptors are known to utilize a number of different compounds for light absorption, including the use of such compounds as flavins, linearized tetrapyrroles (bilins), and carotenoids. Recently, a novel class of photoreceptors that use vitamin B12 (cobalamin) as a blue-light-absorbing chromophore have been described. In this study, we analyzed the mechanism by which the vitamin B12 binding photoreceptor AerR controls the DNA binding activity of the photosystem regulator CrtJ. This study shows that a direct interaction between the vitamin B12 binding photoreceptor AerR with CrtJ modulates CrtJ binding to DNA and importantly, the regulatory outcome of gene expression, as shown here with photosystem promoters.

Project description:Background:Vitamin B12 is an essential micronutrient in humans needed for health maintenance. Deficiency of vitamin B12 has been linked to dietary, environmental and genetic factors. Evidence for the genetic basis of vitamin B12 status is poorly understood. However, advancements in genomic techniques have increased the knowledge-base of the genetics of vitamin B12 status. Based on the candidate gene and genome-wide association (GWA) studies, associations between genetic loci in several genes involved in vitamin B12 metabolism have been identified. Objective:The objective of this literature review was to identify and discuss reports of associations between single-nucleotide polymorphisms (SNPs) in vitamin B12 pathway genes and their influence on the circulating levels of vitamin B12. Methods:Relevant articles were obtained through a literature search on PubMed through to May 2017. An article was included if it examined an association of a SNP with serum or plasma vitamin B12 concentration. Beta coefficients and odds ratios were used to describe the strength of an association, and a P?<?0.05 was considered as statistically significant. Two reviewers independently evaluated the eligibility for the inclusion criteria and extracted the data. Results:From 23 studies which fulfilled the selection criteria, 16 studies identified SNPs that showed statistically significant associations with vitamin B12 concentrations. Fifty-nine vitamin B12-related gene polymorphisms associated with vitamin B12 status were identified in total, from the following populations: African American, Brazilian, Canadian, Chinese, Danish, English, European ancestry, Icelandic, Indian, Italian, Latino, Northern Irish, Portuguese and residents of the USA. Conclusion:Overall, the data analyzed suggests that ethnic-specific associations are involved in the genetic determination of vitamin B12 concentrations. However, despite recent success in genetic studies, the majority of identified genes that could explain variation in vitamin B12 concentrations were from Caucasian populations. Further research utilizing larger sample sizes of non-Caucasian populations is necessary in order to better understand these ethnic-specific associations.

Dataset Information

Cobalamin's (Vitamin B12) Surprising Function as a Photoreceptor.

Publications

Cobalamin's (Vitamin B12) Surprising Function as a Photoreceptor.

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