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Printable Handouts
Navigable Slide Index
- Introduction
- Gene repression in cell division (1)
- Early homeotic gene expression patterns
- The polycomb group
- Mutants of polycomb fail to maintain repression
- Transcriptional memory
- Polycomb group genes - repression
- Core functional PcG complexes (1)
- Polycomb targets large regions of the genome
- Lecture structure
- Regulation of PRC2 in drosophila and humans
- PRC2 core subunits in humans
- Histones- carriers of epigenetic information
- Prominent modifications that can occur (1)
- Marking the ‘epigenome’, differential methylation
- Not all histone methyl marks are equal
- Chromodomains bind H3 tail marks
- Differential chromodomain binding
- Core functional PcG complexes (2)
- Targeting of the PcG complexes
- Drosophila PREs are bound by PHO
- Mechanisms involved in targeting
- Mammalian HOX clusters are a key PRC1 target
- A region between HOXD11 and HOXD12
- Human D11.12 is similar to fly PREs (1)
- D11.12 repression requires YY1 sites
- Endogenous D11.12 is occupied by PcG proteins
- Knockdown of Eed in PRC2
- Human D11.12 is similar to fly PREs (2)
- CpG islands and long non-coding RNAs
- Small RNAs specifying repression
- Noncoding RNAs influence chromatin structure
- Dosage compensation in mammals
- lncRNAs may act in trans to regulate chromatin
- Mode of repression – How are genes silenced?
- Gene repression in cell division (2)
- PRC1 in compaction and ubiquitylation (1)
- Prominent modifications that can occur (2)
- PRC1 in compaction and ubiquitylation (2)
- Nucleosome dynamics
- Nucleosome position and epigenetic regulation
- Mobilizing nucleosomes using SWI/SNF
- Blocking nucleosome movement
- Core functional PcG complexes (3)
- In flies, PSC is required for compaction
- Compacting region is not conserved?
- M33 compacts nucleosomes, but Bmi1 does not
- Characteristics of the compaction domain
- Polycomb compaction mediated by charge (1)
- Is compaction biologically relevant?
- Gene silencing by chromatin compaction
- The SIR complex and mating type silencing
- The SIR3 BAH domain and mating type silencing
- Sir3 BAH/NCP complex at 3 Ĺ resolution
- Key features of the structure
- Physical and genetic contacts correlate (1)
- Physical and genetic contacts correlate (2)
- Structural rearrangements in NCP and BAH
- Folding events in Sir3 BAH/NCP complex (1)
- Folding events in Sir3 BAH/NCP complex (2)
- Sir3 BAH / NCP alter structure in complex (1)
- Sir3 BAH / NCP alter structure in complex (2)
- Folding events in Sir3 BAH/NCP complex (3)
- Sir3 BAH changes
- Speculative model
- Summary
- The nucleosome as a silencing machinery
- Polycomb compaction mediated by charge (2)
- Epigenetic memory
- Maintaining gene repression in cell division
- Epigenetic memory of silencing (1)
- PRC2 core subunits in the EED subunit binds K27
- PRC2 subunits in a portion of H3 binds PRC2
- PRC2 will be more active on repressed chromatin
- Does PRC1 stay on chromatin during replication?
- Are repressed regions ‘bookmarked’ by proteins?
- Lecture summary
- Acknowledgments
Topics Covered
- Gene repression in cell division
- Early homeotic gene expression patterns
- The polycomb group
- Mutants of polycomb fail to maintain repression
- Transcriptional memory
- Core functional PcG complexes
- Regulation of PRC2 in drosophila and humans
- PRC2 core subunits in humans
- Prominent modifications that can occur
- Chromodomains bind H3 tail marks
- Differential chromodomain binding
- Targeting of the PcG complexes
- Drosophila PREs are bound by PHO
- Mechanisms involved in targeting
- Mammalian HOX clusters are a key PRC1 target
- Human D11.12 is similar to fly PREs
- CpG islands and long non-coding RNAs
- Small RNAs specifying repression
- Noncoding RNAs influence chromatin structure
- Mode of repression
- How are genes silenced?
- PRC1 in compaction and ubiquitylation
- Nucleosome dynamics
- Characteristics of the compaction domain
- Gene silencing by chromatin compaction
- The SIR complex and mating type silencing
- Structural rearrangements in NCP and BAH
- Folding events in Sir3 BAH/NCP complex
- The nucleosome as a silencing machinery
- Epigenetic memory
Links
Series:
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Talk Citation
Kingston, R. (2014, February 4). Maintaining the silenced state of master regulatory genes during development [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 22, 2024, from https://doi.org/10.69645/AEMX4585.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Robert Kingston has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Biochemistry
Transcript
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0:00
So I'll be talking today about
maintaining the silenced state
of regulatory genes
during development.
0:09
For an organism to develop
properly, the initial fertilized egg
has a bunch of master regulatory
genes that are in a naive state.
In order for the organism to develop
appropriate cell types and cell
lineages, in some
cells, those master
regulatory genes need to be held on.
But in most cells, those
master regulatory genes
need to be held off.
This is a classic problem
in epigenetic regulation.
Exactly the same DNA sequence
is found on the master
regulatory genes, but
in some gene sets,
sequence is kept in an on
state throughout the entirety
of development.
Whereas in other cell
lineages, that set of genes
is kept in an off state.
So to understand how we can
have a fertilized egg create all
of the different body parts
that create a normal organism,
we have to understand how you can
have a regulated state that can be
inherited from one cell
division to the next.
So today I will focus on the
repressive side of that equation.
How do you repress
a gene and then keep
it repressed for all different
levels of cell division?
1:26
This is a problem that's been
appreciated for a long time,
and it's been studied very
thoroughly over the last 80 years.
The studies initiated
by understanding
how Drosophila, the
fruit fly, develops.
In the fruit fly, you need to
go from an embryo to a fly.
And which part of the fly is going
to be which is established early
on in the embryo and
then is remembered
as the embryo becomes
the intact fly.
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