This was found out with yeast genetics The two mating types HML\u03b1 HMRa loci must

This was found out with yeast genetics the two mating

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This was found out with yeast genetics. The two mating types, HMLα & HMRaloci, must besilenced or else the yeast cells would be diploid α/a couldn’t mate. Silencer sequences represstheir transcription and mutations of H3 & H4 affect this silencing. Centromeres & telomeres arein a silent state. The factors involved: RAP1binds to DNA in the region of the silencer and interacts with SIRproteins at the telomeres and HMRa & HMLα. These interactions change the chromatinconfiguration around those regions as SIR2deacetylates the histone tails → enhancescondensation and recruits more SIR2 → transcription is then blocked. SIR1 cooperates withRAP1 and SIR3 & 4 bind to histone tails H3 & H4 and recruit SIR2. Transcriptional repressors may act through histone deacetylation complexes (HDACs). A TFknown as Ume6has a DNA-binding domain and interacts with an upstream repression site(URS). The protein brings in a large multi-protein complex that changes chromatinconfiguration. The complex interacts with Sin3which recruits Rpd3(deacetylase activity). Allhistone tails in proximity are deacetylated. Transcriptional activators recruit histone acetyl transferases (HATs). The activation domain ofGcn4interacts with Gcn5→ acetyl transferase. Chromatin configuration is opened up andtranscription is enhanced. Histones are an important mediator of how gene expression occurs. Specific residues aremodified on H2, H3 & H4 (histone code). Phosphorylation and methylation can have botheffects as methylation on H3 K4 → ACTIVE and methylation on H3 K9 → INACTIVE. Euchromatinis delicate/thread-like, is abundant in actively transcribing cells and representsDNA that is unwound to provide a transcriptional template. Heterochromatinis condensed,localised near the nuclear pores (nuclear periphery) and transcriptionally inactive. Heterochromatin can spread along specific regions of the genome. Heterochromatin protein 1(HP1)recognizesH3K9me3(trimethylation on lycine 9) and brings inhistonemethyltransferaseswhich propagate the same mark → spreading of the heterochromatin.Antibodies against modified histone tails can be used for ChIP. Immunoprecipitation =antibodies linked to agarose beads. Next-gen sequencing used to study the bound DNA. Females inactivate randomly 1 X chromosome (Barr Body)and that chromosome lacksacetylation marks which are typical for transcriptional activation. Having too manychromosomes is lethal so necessary to shut down all the ‘extra’ ones. After the 1stdecision, all thecells know which X was inactivated. The XISTlocus is responsible by spreading along thechromosome. Epigeneticmarks have to be propagated → changes in gene expression that areindependent of the DNA sequence like inactive X, homeotic transformations, DNA methylation.
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