Langman Embryology Notes

Jaymee B. Quindara RN

1
Chapter 1: Introduction
Regulation and Signalling

to

Molecular

Introduction
23, 000 gees in the human genome.
Gene expression regulation:
o Different genes may be transcribed
o Nuclear DNA transcribed from a
gene may be selectively processed
to regulate RNAs reach the
cytoplasm to become mRNA
o mRNAs
may be
selectively
translated
o proteins made from the mRNA may
be differentially modified.
Gene Transcription
Genes are contained in chromatin (DNA and
histone).
Nucleosome- basic unit structure of a
chromatin.
Each nucleosome is composed of octomer of
histone protein and 140 pairs of DNA.
Nucleosomes themselves are joined into
clusters by binding of DNA existing
between nucleosomes (linker DNA) with
other histone proteins (H1 histones)
Nucleosome keep DNA tightly coiled to
avoid being transcribed.
Chromatin appears beads of nucleosome on
a string of DNA referred as Heterochromatin
in its inactive form.
Euchromatin- uncoiled active form in
which transcription can occur.
Gene reside within the DNA strand
Exons- regions in the DNA strand which
can be translated into proteins
Introns- regions in the DNA strand which
are interspersed between exons and which
are not transcribed into proteins
Promoter region- binds RNA polymerase
for the initiation of transcription. Contains
the sequence TATA TATA box
Transcription initiation site- the first
nucleotide of a transcribed DNA sequence

where RNA polymerase (DNA-DIRECTED

RNA POLYMERASE) begins synthesizing
the RNA transcript.
Translation initiation site- designate the 1st
amino acid in the protein
translation termination codon; and a 3
untranslated region that includes a sequence
(the poly A addition site) that assists with
stabilizing the mRNA, allows it to exit the
nucleus, and permits it to be translated into
protein.
DNA is transcribed from 5 to 3
RNA polymerase requires additional
proteins called transcription factors.
Transcription factors have a specific
DNA-binding domain and transcripting
doimain that activates or inhibits
transcription of gene whose promoter or
enhancer it has bound. TrF activates gene
expression by causing DNA nucleosome
complex to unwind, by releasing the
polymerase so that it can transcribe the DNA
template and prevent new formation of
nucleosome.
DNA binding domain- is a protein structure
that has a high affinity for DNA, and so
binds to it when the two molecules are in the
same vicinity.
Transcripting domain- are regions of a
transcription factor which in conjunction
with a DNA binding domain can activate
transcription from a promoter by contacting
transcriptional
machinery
(general
transcription factors + RNA Polymerase)
either directly or through other proteins
known as co-activators.
Enchancer- are regulatory elements of
DNA that activate utilization of promoters to
control their efficiency and the rate of
transcription from the promoter. Enhancers
can reside anywhere along the DNA strand
and do not have to reside close to a
promoter. Like promoters, enhancers bind
transcription
factors
(through
the
transcription
factors
transactivating

Langman Embryology Notes

Jaymee B. Quindara RN

2
domain) and are used to regulate the timing
of a genes expression and its cell-specific
location. Enhancer act by altering chromatin
to exose the promoter or by facilitating
binding of RNA polymerase.
Silencers- inhibit transcription. Allows
transcription factor to activate one gene
while silencing another by binding to
different enhancers.
Transcription factors themselves have a
DNAbinding domain specifi c to a region of
DNA plus a transactivating domain that
binds to a promoter or an enhancer and
activates or inhibits the gene regulated by
these elements.
DNA Methylation
Methylation of cytosine base of promoter
regions of gene repress transcription of
those genes.
DNA Methylation is also responsible for
genomic imprinting in which only one gene
inherited from the father or the mother is
expressed while the other gene is silenced.
Methylation silences DNA by inhibiting
binding of transcription factors or by
altering histone binding resulting in
stabilization of nucleosomes and tightly
coiled DNA that cannot be transcribed.
* Genes in different types of cells are
repressed by methylation, such that
muscle cells make muscle proteins
(their promoter DNA is mostly
unmethylated), but not blood proteins
(their DNA is highly methylated). In
this manner, each cell can maintain its
characteristic differentiated state.
Other
Regulators
of
Gene
Expression
Nuclear RNA (nRNA) or premessenger
RNA initial transcript of a gene. No longer
than RNA because the introns are spliced
out as it moves from the nucleus to the
cytoplasm.
Splicing process provides a means for cells
to produce different protein from a single
gene.

Alternative splicing- splicing exons in

different patterns by removing introns.
Spliceosomes complexes of small nRNA
and protein that recognize specific sites at
the 5 and 3 ends of the nRNA that carries
the process of splicing.
Splicing isoforms- proteins derived from
the same gene. Also called as splice variants
or alternative splice forms.
These gives the chance for different cells to
use the same gene to make specific gene for
that cell type.
Even if protein is translated ther may be
post-translational modifications that affect
its function.
Induction and Organ Formation
Induction- process by which one group of
cell or tissues causes another set of cells or
tissue to change their fate.
Inducer- cell or tissue type that produces a
signal
Responder- cell or tissue that reacts to the
signal.
Competence- capacity to respond to a signal
which requires competence factor for the
activation of a responding tissue.
Epithelial -Masenchymal interaction
Epithelial- Epithelial interaction
Crosstalk- sending of signal back and forth
is essential for differentiation to continue.
Cell Signalling
Essential for induction, competence, and
crosstalk.
Paracrine
interactionlines
of
communication in which proteins synthesize
by one cell diffuse over short distances to
interact with other cell.
Juxtracrine interaction does not include
diffusible proteins.
Paracrine
factor/
Growth
and
Differentiation
Factors
(GDFs)

diffusible proteins responsible for paracrine

signalling.

Langman Embryology Notes

Jaymee B. Quindara RN

Signal Transduction Pathways

Paracrine Signalling
Paracrine factors act by signal transduction
pathways either by activating a pathway
directly or by blocking the activity of an
inhibitor of a pathway.
Signal transduction pathway include a
ligand which is a signalling molecule and a
receptor.
The receptor spans the cell membrane and
has extracellular domain (ligand-binding
region), transmembrane domain and
cytoplasmic domain.
Ligand receptor conformational
change activation of cytoplasmic domain

confer enzymatic activity (Kinase)

phosphorylate other proteins as a substrate
activation of the proteins cascade of
protein phosphorylation activation of a
transcription factor activate of inhibit
gene expression.
In some pathways one proteins inhibits
another that in turn activate another.
Juxtracrine Signaling
Mediated through signal transduction
pathways but does not involve diffusible
factors.
Protein on one cell surface interacts with a
receptor in a process analogous to paracrine
signalling.
Notch pathway