Date of Award
Master of Arts (MA)
Dr. Elaine Lahue
Introduction: Gene silencing is a normal process in every cell and is required for cells to have different functions. Mis-regulation of silencing can affect cell-cycle regulation, differentiation, and genome stability, all of which can lead to developmental defects and cancer . Heterochromatic or silenced regions are highly condensed and transcriptionally inactive, whereas euchromatin is less condensed and transcriptionally active. Heterochromatic gene silencing occurs when chromosome domains are packaged into specialized structures that limit access of DNA binding proteins, including transcription factors, to the regulatory regions as well as coding regions of genes . For example, the telomeres and silent mating-type loci in Saccharomyces cerevisiae, which are normally in a silent state, consist of a repressive chromatin structure composed of nucleosomal core histones and nonhistone chromatin components, including the Sir (silent information regulators) silencing complex (Figure 1) . Rap1 probably initiates assembly at telomeres when it binds to a 300 bp region of C1-3A repeats on single stranded DNA. Rap1 is thought to recruit Sir4, which recruits the 2 deacetylase Sir2, that enables Sir3 and Sir4 to bind hypoacetylated histone N-terminal tails . The process of heterochromatin spreading based on interactions between the Sir proteins makes approximately 2-4 kb of DNA from the ends of chromosomes inaccessible until the Sir proteins are removed (Figure 1) . The assembly of silencing proteins is thought to form a cap-like structure that protects telomeres and serves to maintain a heterochromatic state . Recently, Kamakaka and others have questioned the traditional model of stably-bound non-histone components as necessary for silencing maintenance, asserting that these proteins are in a constant state of flux based on competition for binding between activators and repressors . Supporting evidence for this model includes fluorescence recovery after photobleaching (FRAP) studies of a key component of condensed DNA, Heterochromatin protein 1 (HP1), that show a fusion protein of HP 1-green fluorescence protein in ex-vivo resting murine T cells is almost equally mobile within heterochromatin as it is within euchromatin .
Smith, Jennie C., "SUB2 helicase is a regulator of heterochromatic silencing in Saccharomyces cerevisiae." (2004). Student Work. 3383.
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