Topic 26, Chromatin remodeling

Topic 26, Chromatin remodeling - Topic 26: Chromatin...

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Topic 26: Chromatin remodeling
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Learning objectives Be able to: Define the following terms: heterochromatin, euchromatin, acetylation, methylation, epigenetics, fusion protein, yeast-two hybrid assay Describe how acetylation and methylation of histone tails affect chromatin structure (slides 13-18) Describe and differentiate between the 2 main methods used to make DNA more accessible to transcription (nucleosome modification and chromatin remodeling) Also, how nucleosomes are changed by these methods Describe the purpose and methodology of the Yeast Two- Hybrid Assay (slides 31-38)
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The big picture of transcription You didn’t forget that eukaryotic DNA is wrapped around histones, did you? So how does the transcriptional machinery get access to the DNA if it is already highly associated with other proteins (histones)? DNA replication has the same problem, but we’ll discuss how transcription overcomes the problem as a model for both scenarios
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Review of topic 12 What parts make up a histone? What differentiates a histone from a nucleosome?
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Two main types of chromatin Chromatin: DNA+ associated proteins in a condensed state 1) Heterochromatin: more dense DNA, less accessible for RNA transcription Mostly repeat sequences, few genes (low activity) 2) Euchromatin: less dense DNA, more available for RNA transcription Mostly gene sequences; (potentially) highly active genes
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Figure 6.05: Electron micrograph of a liver cell nucleus. © Phototake, Inc./Alamy Images rRNA transcription/assembly
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2 main ways to make a DNA sequence more accessible to transcription: 1) Chromatin remodeling—moving histones to new locations on the DNA molecule --Displace from molecule, or translocate to new position on same molecule 1) Nucleosome modification—acetylation or methylation of basic amino acids in the histone tails (nucleosome does not move) --If you remove the + charge, the DNA wound around the histone becomes more loose
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Models are not mutually exclusive In other words, both mechanisms (remodeling and modification) can be used at the same time on a single gene
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Model of nucleosome dynamics during transcription of a yeast gene: Preview Workman J L Genes Dev. 2006;20:2009-2017 A. DNA is not being transcribed B. Two histones completely removed ( remodeling ), one upstream and another one at transcriptional start site C. RNA pol II can now bind to Initiator. Note how C-Terminal Domain (CTD) bends around to the leading edge D. CTD recruits h istone a cetylt ransferases (HATs) to modify nucleosomes before RNA pol II reaches that section of DNA. Note how histone is partially disassembled due to acetylation. Histone is not completely removed, but some components are removed .
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Nucleosomes are remodeled by Swi/Snf complexes Nucleosomes are modified by acetylases, methylases, etc.
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Nucleosome Modification: change structure of the nucleosome, but don’t actually move it
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Figure 16.59: Schematic representation of euchromatin and heterochromatin as
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Topic 26, Chromatin remodeling - Topic 26: Chromatin...

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