Chromatin structure: intro
Based on materials by Irina Zhegalova, Skoltech
Levels of organization in space
Yadav et. al, 2018. Science
C-based methods
Dekker et al., 2002. Science
Chromatin matrix
Imakaev et al., 2012. Nature Methods; Lieberman-Aiden et al., 2009. Science
3D genome
figure by S. Ulianov
TADs - Topologically Associated Domains
3D genome
Structure
Compartments
0.5-10 Mb, Hi-C
0.1-1 Mb, Hi-C, 5C
50-500 kb, Hi-C, 4C, Capture-C
0.007-0.2 mkm2, Oligopaint-FISH
100-1000 nm2, ICH, Chrom-EMT
TADs
Loops
Nanodomains
Clutches
Putative functions
Editing strategy
Spatial segregation of active and inactive chromatin
Spatial insulation of neighboring genome loci and their regulatory systems
Spatial insulation of neighboring genome loci and contacts between regulatory regions
Unknown
Unknown
Unknown
Unknown
Unknown
Mutations and rearrangements of CBSs
Same as for TADs + CTCF recruitment
Size and assay
Identified by C-methods
Identified by microscopy
figure by S. Ulianov
Trans-contacts
Bonev et al., 2016 Nature Reviews Genetics ; Hoencamp, 2021. Science
Chromosome territories
Hi-C maps for chr 1, 2, 3 demonstrating territoriality:
Falk et al., 2019. Nature
Compartments
Active promoters: H3K4me3, H3K9Ac
Active enhancers: H3K27Ac, H3K4me1
Repressors: H3K9me3, H3K27me3
Transcribed gene bodies: H3K36me3
Marchal, et al., 2019. Nature Reviews Molecular Cell Biology; figure by S. Ulianov
Phase separation
Feric et al., 2021. Trends in Cell Biology
Extrusion
SMC1
SMC3
RAD21
SA1
or SA2
Cohesin
CTCF
CTCF sites of the
same orientation
CTCF sites of
divergent orientation
CTCF sites of
convergent orientation
Extrusion
Extrusion
Zhang et al., 2022. NatRevImmunology ; Li et al., 2020. Nature
TAD + TAD = compartment?
Starring:
cohesin as an Extruder CTCF as a Barrier
Knockout of CTCF results in TADs lost but not compartments
Compartments are less conserved across cell types than TADs
Phenotypic changes are more frequently associated with compartment repositioning than with structural disruption of loops or TADs
figure by S. Ulianov
Loops
Different names for the same feature: loops, dots, enriched contacts
Rao et al., 2014. Cell figure by S. Ulyanov
If there is no CTCF
Kristian Jeppsson, 2022 Science Advances; Heger et al., 2012. PNAS
TADs vs loops
What do they have in common?
Chromatin Zoo
© 2023 I. Zhegalova OMICS
Dekker, J. et al., 2015. FEBS letters; Hoencamp, 2021. Science
Chromatin structure: methods besides Hi-C
Micro-C nucleosome scale
Hsieh et al., 2020. Molecular cell
Single cell Hi-C
Flyamer et al., 2017. Nature
Borders are stable
Ulianov et al., 2021. Nature Communications
Red-C
RedChIP Red-C RADICL-seq
RNA-DNA SPRITE
Gavrilov et al., 2020. Nucleic Acids Research
RNA-DNA SPRITE
RNA-DNA SPRITE
Quinodoz et al., 2021. Cell
Levels of organization in space
Yadav et. al, 2018. Science
... and time
Cuvier and Fierz, 2017. Nature Reviews Genetics
Microscopy - PALM
Xie et al., 2020. Nature Methods
Oligopaint
optical reconstruction of chromatin architecture (ORCA)
method that uses
Oligopaint probes to label the genome with resolution reaching 2 kb
Mateo et al., 2021. Nature Protocols
ORCA
Mateo et al., 2021. Nature Protocols