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Silent Information Regulator (SIR) proteins are proteins conserved from yeast to humans that are involved in organizing heterochromatin at telomeres, rDNA and at silent loci including, in yeast, the hidden mating type loci. SIR family genes encode catalytic and non-catalytic proteins that are involved in de-acetylation of histone tails and the subsequent condensation of chromatin around a SIR protein scaffold. ==History== SIR proteins have been identified in many screens, and have historically been known as SIR〔 (silent information regulator), MAR〔 (mating-type regulator), STE (sterile), CMT〔 (change of mating type) or SSP (sterile suppressor) according to which screen led to their identification. Ultimately, the name SIR had the most staying power, because it most accurately describes the function of the encoded proteins. One of the early yeast screens to identify SIR genes was performed by Anita Hopper and Benjamin Hall, who screened with mutagenesis for alleles allow sporulation in a normally sporulation-deficient heterothallic α/α (''ho/ho MATα/MATα''). Their screen identified a mutation in a novel gene that was not linked to ''HO'' that allowed the α/α diploid to sporulate, as if it were an α/a diploid, and inferred that the mutation affected a change in mating type by an ''HO''-independent mechanism. Later, it was discovered at the CMT allele identified by Hopper & Hall did not cause a mating type conversion at the MAT locus, but rather allowed the expression of cryptic mating type genes that are silenced in wild-type yeast.〔 In their paper clarifying the mechanism of the CMT mutation, Haber and George acknowledge the contribution of Amar Klar, who presented his MAR mutant strains that had similar properties as the CMT mutants at the Cold Spring Harbor Laboratory yeast genetics meeting, which led Haber and George to consider the hypotheses that the ''cmt'' mutants may act by de-repressing silent information. In the same year that Haber & George demonstrated that the ''cmt'' mutant restores sporulation by de-repressing hidden mating type loci, two other groups published screens for genes involved in the regulation of silent mating type cassettes.〔 The first study, performed by Amar Klar, Seymour Fogel and Kathy Macleod, identified a mutation in a spontaneous a/a diploid that caused the products of sporulation to be haploids with an apparent diploid phenotype, as assayed by ability to mate. The authors reasoned that the mutation caused the de-repression of then-recently appreciated silent mating type loci HMa and HMα, which would allow an a/a diploid to sporulate and would cause haploid segregants inheriting the mutant allele to behave as a/α diploids despite being haploid.〔 The authors named the mutation MAR for its apparent role in mating type regulation, and were able to map the mutation to chromosome IV, and determined that it was located 27.3 cM from a commonly used ''trp1'' marker.〔 A few months later, Jasper Rine and Ira Herskowitz published a different screen for genes that affect the ability of yeast to mate, and ultimate discovered the gene family that they called SIR, a name that remains in the modern parlance.〔 Unlike the Klar et al. screen that identified a mutant by its inability to mate, Rine & Herskowitz took a more directed approach towards discovering factors responsible for mating type silencing. Specifically, Rine & Herskowitz reasoned that a haploid yeast cell with a recessive mutation in matα1 could be complemented if the silent copy of MATα were de-repressed. Starting in a ''ho matα1'' haploid strain, Rine & Herskowitz screen mutants arising from mutagenesis and identified five mutants that restored a MATα phenotype in matα cells, but were not linked to the MAT locus and did not cause a gene conversion between the HMα locus and matα.〔 These mutants, they reasoned, were responsible specifically for silencing the cryptic mating type genes. Eventually, all of the mutants resulting from the original Hopper & Hall screen as well as the later Rine & Herskowitz screen and the Klar et al. screen were characterized and mapped, and it was shown that the causative genes were actually the same. In fact, the genes that are now referred to as SIR1-4 have at one time been referred to as MAR, CMT or STE according to the screen that identified the mutants. Although Klar, Hartwell and Hopper identified mutations in SIR genes and applied other names to the genes before Rine performed his screen, the SIR name was eventually adopted because Rine eventually identified the most complete set of functionally related genes (SIR1-4), and because the work by Rine and Herskowitz most accurately described the function of the SIR family genes.〔 Later it would be shown that in yeast and in higher organisms, SIR are important for transcriptional regulation of many types of chromatin, and are uniquely involved in mating type regulation. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「SIR protein」の詳細全文を読む スポンサード リンク
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