Histone Modifications & Epigenetics

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Department
Biochemistry & Molecular Bio.
Course
BIOCHEM 524
Professor
David Gross
Semester
Spring

Description
Feb 21 Notes • Histone mods can spread o acetylation occurs during transcription and is removed after o methylation occurs after transcription and prevents expression • Code-reader complex o scaffold protein holds protein modules that bind to specific histone mods on nucleosome o it then attracts other components such as a protein complex w/ catalytic activities & additional binding sites o this leads to gene expression, gene silencing, or other biological functions • Histone mods can spread o code-reader proteins can recruit code-writer proteins o if the mark that is read to recruit the code-reader protein is the same as the mark that is written by the code-writer protein, the process can occur again and spread across nucleosomes • Code-writer complexes o association of reader-writer complexes w/ chromatin remodeling complexes can drive condensation of chromatin • Barrier proteins o prevent overspreading of heterochromatin (silenced regions) o histone acetylases can act as barrier proteins & prevent spreading of methylation by reader-writer complexes o can either be a physical barrier to methylation or modify the histones in a competitive way • Many histone subtypes o variation for each core histone except H4 exist  these contribute to the histone code o there can be different types of N-terminal tail sequences & changes in core histone-folds o Ex.  H3.3 – causes transcriptional activation  CENP-A(H3 mod) – centromere function & kinetochore assembly  H2AX – DNArepair & recombination  H2AZ – gene expression, chromosome segregation  macroH2A(H2Amod) – transcriptional repression, X-chromosome inactivation • Remodeling complexes o useARP hydrolysis to alter chromatin composition o w/ histone chaperones can exchange histone components or even entire core o chaperones keep histones soluble until recruited into nucleosome • Histone variants cause different mechanisms to occur o CENP-A(H3 mod) helps recruit kinetochore components  the mod allows kinetochore components to attach to different recruited proteins o in yeast a specific 125 bp sequence sufficient to generate centromere (enough to recruit 1 histone octomer) • Centromeres o centromeres can extend over 1000kb & don’t need to contain specific centromeric sequence (flies & humans example)  instead simple repeat regions where centromeres form (alpha satellite DNA) o in this case centromeres defined more by protein composition than DNAsequence  regions of alpha satellite DNAcan exist w/o centromeric proteins  neocentromeres can form @ non-alpha satellite regions (rare) o longer centromeres consist of repeating regions w/ CENP-Ahistones & dimethylated normal H3’s (@ K4) • Heterochromatin o pericentric heterochromatin are compacted chromatin on the edge of the heterochromatic region (outli
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