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Navigable Slide Index
- Histone modifications & prospects
- The nucleosome (1980s)
- H4 isoforms resolved by electrophoresis
- Antibodies can be raised by immunization
- Antibodies provide exquisitely sensitive reagents
- Modifications associated with functional effects
- Polygene chromosomes stained with Hoechst
- Female Xs show no selective labeling
- Immunolabeling with anti-MLE and anti-H4acK16
- Instar neuroblasts stained with Hoechst
- Neuroblasts selectively labeled with antibodies
- Modifications to individual amino acids
- The nucleosome carries signaling information
- Nucleosome surface markers and signaling
- Decoding the Nucleosome
- Histone modifying enzymes have been identified
- Enzyme families that modify histone tails
- Binding proteins influence chromatin structure
- Residue-specific, histone modifications
- H3K9 is methylated by SET-domain enzymes
- Complex array of modifications on Histone tails
- How the tails are coated with such an array
- Modifications on the same amino acid differ
- Arginines can be methylated in three different ways
- Lysine modifications
- Atomic structures of methylated lysines
- H4 isoforms have different distributions
- Rapid turn-over by modifying/de-modifying actions
- H4 isoforms resolved by electrophoresis
- Turnover influence by a variety of factors
- Factors that influence histone tail acetylation
- "cross-talk" between histone modifications
- Histone marks may be removed or hidden
- HP1 binds to H3 by (HMT) SUV39
- Acetylation & phosphorylation block methylation
- Modifications of H3 can block methylation
- Histone modifications provide "epigenetic code" ?
- Epigenetic/histone code hypothesis
- Difference to nucleosome "signaling" hypothesis
- Properties of an epigenetic code
- Roles of chromatin modification
- Distinguishing long and short term effects of H.M.
- How should we look for an epigenetic code?
- ChIP can be used to show modification distribution
- ChIP assay
- ChIP used to study transcriptional activity
- ChIP shows effects of acetylation changes
- ChIP can be combined with microarray analysis
- The ChIP-chip procedure
- Histone acetylation and H3K4 tri-methylation
- Correlation of H3K4me3 & individual genes
- Both marks are enriched at promoters in yeast
- Summarization of results from the Young lab
- H.M. plays crucial roles in transcription, but...
- So where should we look?
- Heterochromatin staining
- Heterochromatic regions are marked by H.M.
- H4K20me3 located at centromeres of autosomes
- Euchromatic domains are also marked by H.M.
- Antibodies show banding along chromosome arms
- Epigenetic mapping is in its infancy
- Epigenetic marking of large chromosome domains
- Summary
- Questions to address in the near future
Topics Covered
- Enzyme-catalyzed modification of the N-terminal tail domains of core histones provides an array of marks across the nucleosome surface and a source of epigenetic information
- this information influences protein-protein interactions during short-term regulation of ongoing transcription and is a means of maintaining or modifying patterns of gene expression from one cell generation to the next
- cellular memory
- histone modifications may constitute a heritable epigenetic code that acts in concert with the genetic code as a long-term regulator of gene expression
Talk Citation
Turner, B. (2015, January 19). Histone modifications and prospects for an epigenetic code [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 27, 2024, from https://doi.org/10.69645/MJPE9962.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Bryan Turner has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Histone modifications and prospects for an epigenetic code
A selection of talks on Biochemistry
Transcript
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0:00
Histone modifications and prospects for an epigenetic code.
This talk will give an overview of the wide range
of histone modifications that are now known to exist,
and discuss the possibility that they might operate as an epigenetic code,
something that works in parallel with the genetic code to regulate chromatin function.
I plan to take a historical approach to the subject and explain the origins of
the idea that histone modifications might operate as units of epigenetic information.
By doing this, I hope to be able to illustrate
how a possible epigenetic code might operate,
and what we should expect it to do.