Summary Differential Gene Expression in Developmental Biology Notes
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Course
Advanced Developmental Biology (MCBG3034A)
Institution
University Of The Witwatersrand (wits)
Book
Developmental Biology
These notes summarize all the concepts in Chapter 3 of the textbook: Developmental Biology (12th edition). They are concise and very detailed to aid in understanding. Relevant diagrams and images are also included to further enhance the topics. The notes are A4 and in pdf format. The end of the not...
Developmental Biology 12th Edition By Michael J.F. Barresi; Scott F. Gilbert
Developmental Biology 12th Edition By Michael J.F. Barresi; Scott F. Gilbert
Test Bank for Developmental Biology 12th Edition Barresi Questions With Complete Solutions Verified
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Advanced Developmental Biology (MCBG3034A)
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• The dividing cells of the fertilized egg form three distinct embryonic germ layers. Each of the germ layers
gives rise to myriad differentiated cell types (only a few representatives are shown here) and distinct
organ systems.
• The germ cells (precursors of the sperm and egg) are set aside early in development and do not arise
from any particular germ layer.
• The selective production of different proteins within cells creates cellular diversity.
• As the single-celled zygote divides to start the generation of all the cells making up an organism,
differences in the expression of genes in these cells govern maturation toward distinct cell types.
• Many regulatory mechanisms targeting DNA access, RNA production and processing, and protein
synthesis and modification lead to this differential gene expression.
• They include using a specific repertoire of transcription factors that bind gene promoters to enhance or
repress transcription, modifying histones to modulate the accessibility of chromatin, and degrading and
alternative splicing of RNA to change the coded message for different protein construction.
• In addition, translational controls and posttranslational modifications of proteins as well as changes in
protein transport affect what proteins are created and where they function.
• Use of these numerous mechanisms at different times and in different cells fuels the creation of different
cell types as the embryo develops.
• There are three postulates of differential gene expression:
1. Every somatic cell nucleus of an organism contains the complete genome established in the fertilized
egg. In molecular terms, the DNAs of all differentiated cells are identical.
2. The unused genes in differentiated cells are neither destroyed nor mutated; they retain the potential
for being expressed.
3. Only a small percentage of the genome is expressed in each cell, and a portion of the RNA
synthesized in each cell is specific for that cell type.
• Gene expression can be regulated at four levels such that different cell types synthesize different sets of
proteins:
→ Differential gene transcription regulates which of the nuclear genes are transcribed into nuclear RNA.
→ Selective nuclear RNA processing regulates which of the transcribed RNAs (or which parts of such a
nuclear RNA) are able to enter into the cytoplasm and become messenger RNAs.
→ Selective messenger RNA translation regulates which of the mRNAs in the cytoplasm are translated
into proteins.
→ Differential protein modification regulates which proteins are allowed to remain and/ or function in the
cell.
,MODULATING ACCESS TO GENES
• A fundamental difference distinguishing most eukaryotic genes from prokaryotic genes is that
eukaryotic genes are contained within a complex of DNA and protein called chromatin.
• The protein component constitutes about half the weight of chromatin and is composed largely of
histones.
• The nucleosome is the basic unit of chromatin structure. It is composed of an octamer of histone
proteins (two molecules each of histones H2A, H2B, H3, and H4) wrapped with two loops containing
approximately 147 base pairs of DNA.
• Much of the time, the nucleosomes appear to be wound into tight structures called solenoids that are
stabilized by histone H1.
• This H1-dependent conformation of nucleosomes inhibits the transcription of genes in somatic cells by
packing adjacent nucleosomes together into tight arrays that prevent transcription factors and RNA
polymerases from gaining access to the genes.
• Chromatin regions that are tightly packed are called heterochromatin, and regions loosely packed are
called euchromatin.
• One way to achieve differential gene expression is by regulating how tightly packed a given region of
chromatin may be, thereby regulating whether genes are even accessible for transcription.
LOOSENING AND TIGHTENING CHROMATIN: HISTONES AS GATEKEEPERS
• Histones are critical because they appear to be responsible for either facilitating or forbidding gene
expression.
• Repression and activation are controlled to a large extent by modifying the “tails” of histones H3 and
H4 with two small organic groups: methyl (CH3) and acetyl (COCH3) residues.
• In general, histone acetylation—the addition of negatively charged acetyl groups to histones—
neutralizes the basic charge of lysine and loosens the histones, which activates transcription.
• Enzymes known as histone acetyltransferases place acetyl groups on histones (especially on lysines in
H3 and H4), destabilizing the nucleosomes so that they come apart easily (become more
euchromatic).
• As might be expected, then, enzymes that remove acetyl groups—histone deacetylases—stabilize the
nucleosomes (which become more heterochromatic) and prevent transcription.
, • Histone methylation is the addition of methyl groups to histones by enzymes called histone
methyltransferases.
• Although histone methylation more often results in heterochromatic states and transcriptional
repression, it can also activate transcription depending on the amino acid being methylated and the
presence of other methyl or acetyl groups in the vicinity.
⤷ For instance, acetylation of the tails of H3 and H4 along with the addition of three methyl groups
on the lysine at position four of H3 (i.e., H3K4me3; remember that K is the abbreviation for
lysine) is usually associated with actively transcribed chromatin.
⤷ In contrast, a combined lack of acetylation of the H3 and H4 tails and methylation of the lysine in
the ninth position of H3 (H3K9) is usually associated with highly repressed chromatin.
• Lysine methylations at H3K9, H3K27, and H4K20 are often associated with highly repressed
chromatin. Modifications of such residues regulate transcription.
• If methyl groups at specific places on histones repress transcription, getting rid of these methyl
moieties should be expected to permit transcription.
⤷ That has been shown to be the case in the activation of the Hox genes, a family of genes that are
critical in giving cells their identities along the anterior-posterior body axis.
⤷ In early development, Hox genes are repressed by H3K27 trimethylation (the lysine at position 27
on histone 3 has three methyl groups: H3K27me3).
• In differentiated cells, however, a demethylase specific for H3K27me3 is recruited to these regions,
eliminating the methyl groups and enabling access to the gene for transcription.
ANATOMY OF THE GENE
• A fundamental feature that distinguishes eukaryotic from prokaryotic genes (along with eukaryotic
genes being contained within chromatin) is that eukaryotic genes are not co-linear with their peptide
products.
• Rather, the single nucleic acid strand of eukaryotic mRNA comes from noncontiguous regions on the
chromosome.
• Exons are the regions of DNA that code for parts of a protein; between exons, however, are
intervening sequences called introns that have nothing whatsoever to do with the amino acid
sequence of the protein.
• This gene, which encodes part of the hemoglobin protein of the red blood cells, consists of the
following elements:
─ Enhancer ─ Introns
─ Promoter ─ Translation termination codon
─ Transcription initiation site ─ 3’ UTR
─ 5’ UTR ─ Poly-A signal
─ Translation initiation site ─ Transcription termination sequence
─ Coding exons
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