DNA

1. “REWIRING STEM CELLS: NEW
TECHNIQUE MAY REVOLUTIONIZE
UNDERSTANDING OF HOW GENES
FUNCTION”
AND
“IMPORTANT DISCOVERY FOR
DIAGNOSIS OF GENETIC DISEASES”.
María Angélica Díaz Uribe
Medicine student
III Semester
Molecular Biology

4. INTRODUCTION
news report on genetic studies about
effective method to identify the working
of genes in cell differentiation and
possible causes of genetic syndromes
attributed to the three-dimensional
organization of chromatin.

5. “REWIRING STEM CELLS:
NEW TECHNIQUE MAY
REVOLUTIONIZE
UNDERSTANDING OF HOW
GENES FUNCTION”

6. “REWIRING STEM CELLS: NEW TECHNIQUE MAY REVOLUTIONIZE
UNDERSTANDING OF HOW GENES FUNCTION”
Cell
type in
an
organism expresses a subset of all
the genes that
constitute
the genome of that species.
Each cell type is defined by its
particular pattern of regulated gene
expression. Cell differentiation is
thus a transition of a cell from one
cell type to another and it involves
a switch from one pattern of gene
expression to another.
Cellular differentiation during
development can be
understood as the result
of a gene regulatory network.

7. “REWIRING STEM CELLS: NEW TECHNIQUE MAY REVOLUTIONIZE
UNDERSTANDING OF HOW GENES FUNCTION”
The searches used unfertilised mouse
eggs to generate embryonic stem cells with
a single set of chromosomes, known as
haploid stem cells.
Haploid cells show all of the same
characteristics as stem cells with two sets
of chromosomes, and retain the same full
developmental potential. This cells
facilitates that the process is a bit faster.

8. “REWIRING STEM CELLS: NEW TECHNIQUE MAY REVOLUTIONIZE
UNDERSTANDING OF HOW GENES FUNCTION”
A
transposable
element (TE, transposon or retrotransposo
n) is a DNA sequence that can change its
position within the genome, sometimes
creating or reversing mutations and altering
the cell's genome size. Transposition often
results in duplication of the TE
The researchers used transposons --
"jumping genes"- to make mutations in
nearly all genes. The effect of a mutation
can be seen immediately in haploid cells
because there is no second gene copy.

9. “REWIRING STEM CELLS: NEW TECHNIQUE MAY REVOLUTIONIZE
UNDERSTANDING OF HOW GENES FUNCTION”
They used haploid ESCs to
develop a forward genetics
screen for pluripotency
regulators.
METHODS
A cohort of candidate genes
that promote collapse of
self-renewal was validated.
The conserved zinc finger
protein Zfp706 promotes
differentiation.
Pum1 mediates
posttranscriptional
destabilization of the
pluripotency network.
Identify key players
regulating exit from
self-renewal in ESCs
using a forward
genetic screen in
haploid ESCs.

10. “REWIRING STEM CELLS: NEW TECHNIQUE MAY REVOLUTIONIZE
UNDERSTANDING OF HOW GENES FUNCTION”
PERSONAL OBSERVATION
Circuits self-renewal of embryonic stem cells (ESCs) haploid is a
useful and fast tool for determining the operational work of the
gene, this discovery opens the door for intervention in the
development process and makes possible the understanding of a
large number heart disease, liver problems and cancer.

11. “IMPORTANT DISCOVERY FOR
DIAGNOSIS OF GENETIC DISEASES”.

12. “IMPORTANT DISCOVERY FOR
DIAGNOSIS OF GENETIC DISEASES”.
activity of
genes
controlling
embryonic
development
The threedimensional
organization
of the
chromatin.
The substance distributed in the nucleus of
a
cell
that
condenses
to
form
chromosomes during cell division. The
basic repeating structural (and functional)
unit of chromatin is the nucleosome, which
contains nine histone proteins and about
166 base pairs of DNA

13. “IMPORTANT DISCOVERY FOR
DIAGNOSIS OF GENETIC DISEASES”.
Hox genes encode transcription
factors with crucial roles during
development. These genes are
grouped in four different clusters
names HoxA, B, C,
and D.
Mutations
in
genes
of
the HoxAand D clusters
have
been found in several human
syndromes, affecting in some
cases limb development.

14. “IMPORTANT DISCOVERY FOR
DIAGNOSIS OF GENETIC DISEASES”.
Enhancer
In genetics, an enhancer is a short region
of DNA that
can
be
bound
with proteins (namely,
the trans-acting
factors, much like a set of transcription
factors) to enhance transcription levels
of genes (hence the name) in a gene
cluster. While enhancers are usually cisacting, an enhancer does not need to be
particularly close to the genes it acts on,
and sometimes need not be located on
the same chromosome

15. “IMPORTANT DISCOVERY FOR
DIAGNOSIS OF GENETIC DISEASES”.
Model illustrating how genome topology underlies the tissue-specific regulation
of HoxA genes.
The HoxA cluster is partitioned between two TADs (light blue), physically
segregating3′HoxA from 5′HoxA genes in a mostly cell-type independent manner. In
contrast, the sub-TAD interaction pattern is drastically different in the limb (A) compared
to the head (B).

16. “IMPORTANT DISCOVERY FOR
DIAGNOSIS OF GENETIC DISEASES”.
PERSONAL OBSERVATION
The study reveals that extensive threedimensional chromatin interactions control
the expression of HoxA genes in
developing limbs by forming distinct
topological domains containing limb
enhancers, which interact with each other
and with the topological domains
containing their target genes.

17. MEDICAL UTILITY

18. MEDICAL UTILITY
Achieve a better understanding of
cell differentiation process is
essential for the future of genetic
research and therefore, for medical
progress in search of fighting
diseases current.
studies on the structure and
organization of chromatin are the
beginning to identify the source of
many genetic diseases and
manipulate the genes involved to
prevent.

19. BIBLIOGRAPHY
Rewiring stem cells: New technique may revolutionize understanding of how genes
function, Science Daily; 2014 [cited 2014 january 9]. Available at:
http://www.sciencedaily.com/releases/2014/01/140109132309.htm
Important discovery for diagnosis of genetic diseases. Science Daily; 2014 [january 16].
Available at: http://www.sciencedaily.com/releases/2014/01/140116113512.htm
Leeb M, Dietmann S, Paramor M, Niwa H, Smith A.(2014). Genetic Exploration of the Exit
from Self-Renewal Using Haploid Embryonic Stem Cells. Cell Stem Cell [online]. Availabe at:
http://www.sciencedirect.com/science/article/pii/S1934590913005572
Soizik Berlivet, Denis Paquette, Annie Dumouchel,David Langlais, Josée Dostie, & Marie
Kmita. (2014).Clustering of Tissue-Specific Sub-TADs Accompanies the Regulation
of HoxAGenes in Developing Limbs. PloS Genetics [online] Available
at:http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1004018

20. THANKS