FÁTIMA MANZANO NÚÑEZ
Next step
Elucidation of the cellular
organization of genomes and its
impact on genome regulation and
activity




How is the genome organized in 3D space?
What are the fundamental principles of
organization?
What are the molecular mechanisms that
give rise to the organization patterns?
What are the physiological
consequences of spatial genome
organization?
Loops
LADs
Fig.1 T. Cremer and C. Cremer.
Nature reviews . Vo. 2. 2001
LADs
Only structural
properties?
Low gene expression levels
Nearly 40% of human genome consist on LADs
Lars Guelen et al. Nature. Vo. 453. 2008.
LADs
Study the association of chromatin to any protein
Dam (DNA adenine methyltansferase) + Protein
Methylated regions are amplified (PCR) and analyzed by
high-throughput techniques (microarrays or sequencing).
Alejandro Rodriguez et al. Biochemical Society
Transactions . Vo. 41, p. 6, 2013.
LADs
Dam - Lamin B1
Interaction map
a)High levels of LADs alternate
with low levels. Sharp transitions.
b) and c) LADs vary in size and are
frequently 1 megabase (Mb) in size
or larger
Fig. 1. Lars Guelen et al. Nature. Vo. 453. 2008.
LADs
Fig. 4. Lars Guelen et al. Nature. Vo. 453. 2008.
Loops
Structural elements with regulatory functions
MHC II cluster
Fig. 2. Tom Misteli. Cell. 128, 787–800, 2007
Fig.4. Emanuela V. Volpi1 et al. Journal of
Cell Science 113, 1565-1576 . 2000.
Internal vs.
peripherial
Relative
positions
Translocations
Changes in
transcriptional activity
and gene density
Change the position of genes during differentiation
Fig.2 Masahiko Kuroda et al. Journal
of Cell Science. 117, 5897-5903, 2004.
Functional consequences of Global
chromatin organization
Relative position important
determinant of function
Separate chromosomes into Separate chromosomes into
physical interaction
physical proximity sharing
corregulating gene loci.
transcription sites.
Trans-regulation.
Fig. 3. Tom Misteli. Cell. 128, 787–800, 2007
Tissue-specific proximity of
chromosomes correlates with tissuespecific translocation frequency
Tissue specific
chromosomes organization
Fig. 3. Tom Misteli. Cell. 128, 787–800, 2007
Fig.1. Luis A Parada et al. Genome
Biology, Vo. 5, 7, R44. 2004






Such areas that are nearly the lamina have low gene
density and transcription.
Loops are structural elements with regulatory
functions.
The organization of the genome is related with its
regulation.
The organization of the genome depends of the genes
that are active or inactive, so also of the kind of cell
and its differentiation level.
The organization can follow the internal vs.
peripheral pattern or the relative position model.
Translocations have tissue-specific frequency.
1.
2.
3.
4.
5.
6.
7.
8.
Alejandro Rodriguez et al. The links between chromatin spatial organization and biological
function. Biochemical Society Transactions . Vo. 41, p. 6, 2013.
Emanuela V. Volpi1 et al. Large-scale chromatin organization of the major histocompatibility
complex and other regions of human chromosome 6 and its response to interferon in interphase
nuclei. Journal of Cell Science 113, 1565-1576 . 2000.
Lars Guelen et al. Domain organization of human chromosomes revealed by mapping of nuclear
lamina interactions. Nature. Vo. 453. 2008.
Luis A Parada et al. Tissue-specific spatial organization of genomes. Genome Biology, Vo. 5, 7,
R44. 2004.
Masahiko Kuroda et al. Alteration of chromosome positioning during adipocyte differentiation.
Journal of Cell Science. 117, 5897-5903, 2004.
Shlomit Farkash-Amar et al. Systematic Determination of Replication Activity Type Highlights
Interconnections between Replication, Chromatin Structure and Nuclear Localization. Plos one. Vo.
7 , 11, 2012.
T. Cremer and C. Cremer. Chromosome territories nuclear architecture and gene regulation in
mammalian cells. Nature reviews . Vo. 2. 2001.
Tom Misteli. Beyond the Sequence: Cellular Organization of Genome Function. Cell. 128, 787–800,
2007.