May 2010 Nucleosome Positioning amp Transcription Factor Identification Outline Basic Concept Nucleosome Positioning and Gene Regulation General Transcription Mechanism Genomic Organization of ID: 316430
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Slide1
Zhang ZhizhuoMay 2010
Nucleosome
Positioning
&
Transcription Factor
IdentificationSlide2
Outline
Basic Concept
Nucleosome
Positioning and Gene Regulation
General Transcription Mechanism
Genomic Organization of
Nucleosomes
The Organization of
Nucleosomes
on Genes
Control of DNA Access
Nucleosome
Related TF Identification
Enhancer Identification
Integrating
Histone
Information to Predict TF binding sitesSlide3
Basic Concept
Histone
NucleosomeSlide4
Basic Concept
Histone
Nucleosome
Linker-DNA
DNA between two
nucleosomes
RNA PolyIIAn enzyme catalyzes the transcription of DNATBP
TATA binding protein and a necessary component of RNA polymeraseSlide5
General Transcription Mechanism
”
Bridge
”
Chromatin
remodellingSlide6
General Transcription MechanismSlide7
Genomic Organization of
Nucleosomes
Deposition of
histones
on DNA during DNA replication occurs at random positions?
Not Really!Slide8
Genomic Organization of Nucleosomes
Highly phased or a random continuous distributionSlide9
Genomic Organization of Nucleosomes
Highly phased or a random continuous distribution
Facing inwards or outwardsSlide10
Distance between Positioned nucleosomes
Tend to be fixed distance
short stretches of
linker DNA
165 bp (18 bp linker) in
S.
cerevisiae175 bp (28 bp linker) in D.
melanogaste185 bp (38 bp linker) in humansISWI complex models the spacingLinkers might have regulatory functionsSlide11
The organization of nucleosomes
on genes
Nucleosome
numberingSlide12
The organization of nucleosomes
on genes
Nucleosome
numbering
H2A.Z levels,
acetylation
, H3K4 methylation and phasingSlide13
Nucleosome Positions
Independent positioning
Statistical Positioning
Analog to Roulette wheelSlide14
Nucleosome-Free Region(NFR)
Poly(
dA:dT
) tracts contribute to rigidity
We thought promoter regions would be occluded by
nucleosomes
except when they were activated.But in fact, NFRs demonstrated that open promoter states are stable and common, even at genes that are transcribed so infrequently.Slide15
Nucleosome-Free Region(NFR)
Low basal levels of leaky transcription might have a general housekeeping function
Open architecture of the 5' NFR is necessary for the initial 'pioneering' polymerase or whether transcription itself establishes the NFR from the closed state (after the last transcription)Slide16
Transcription start site selection by
nucleosomes
?
Most promoters seem to lack core promoter elements, including a TATA box, the TFIIB recognition element (BRE), INR, downstream promoter element (DPE) or motif ten element (MTE)Slide17
Control of DNA Access
DNA accessibility without catalysis
thermal fluctuation
energetically less
favourable
towards the midpoint of the
nucleosomeBinding of one factor might stabilize a partially disassembled stateSlide18
Control of DNA Access
DNA accessibility without catalysis
DNA accessibility and
remodelling
complexesSlide19
Control of DNA Access
DNA accessibility without catalysis
DNA accessibility and
remodelling
complexes
Nucleosome
evictionSlide20
Nucleosome
dynamics define transcriptional enhancers.
Nat Genet
42
:343-347.
Genome-wide prediction of transcription factor binding sites using an integrated model.
Genome Biol
11:R7.
Nucleosome
Related TF IdentificationSlide21
Nucleosome
Dynamics Define Transcriptional Enhancers
Monomethylated
H3K4 (H3K4me) : enhancers,
Trimethylated
H3K4 (H3K4me3) :TSS,
Dimethylated H3K4 (H3K4me2) : both the TSS and enhancersSlide22
H3K4me2 are destabilized at AR binding site, but better positioning at flanking loci.
FOXA1 as pioneer factor to stabilize the
nucleosomes
. Slide23
Motif Analysis in the Paired Nucleosome
Regions
Identify
NucleosomeSlide24
Motif Analysis in the Paired Nucleosome
Regions
Identify
Nucleosome
Identify Enhancer RegionSlide25
Motif Analysis in the Paired Nucleosome
Regions
Identify
Nucleosome
Identify Enhancer Region
Motif Analysis in Enhancer RegionSlide26
Genome-wide prediction of transcription factor binding sites using an integrated model
Eight chromatin marks (H3, H3K4me1, H3K4me2, H3K4me3, H3K9me3, H3K36me3, H3K20me3, and H3K27me3) Slide27
Genome-wide prediction of transcription factor binding sites using an integrated modelSlide28
Future work
Finding candidate
nucleosome
organizing factors
Better understand
nucleosome positioningSlide29
Reference
I) NUCLEOSOME POSITIONING.II) NUCLEOSOME REMODELING. BCH 6415.
http://www.med.ufl.edu/biochem/tyang/
http://www.uio.no/studier/emner/matnat/molbio/MBV4230/
Nucleosome
dynamics define transcriptional enhancers, Nature genetics 42 (4): 343-7, 2010 Apr
Nucleosome positioning and gene regulation: advances through genomics, Nature reviews. Genetics 10 (3): 161-72, 2009 MarInducible gene expression: diverse regulatory mechanisms,
Nature reviews. Genetics , 2010 Apr 27
Genome-wide prediction of transcription factor binding sites using an integrated model,
Genome biology 11 (1): R7, 2010 Jan 22
http://en.wikipedia.org/wiki/HistoneSlide30
Q&A