Apoptosis, or programmed cell death, is a normal component of the development and

health of multicellular organisms. Cells die in response to a variety of stimuli and during
apoptosis they do so in a controlled, regulated fashion. This makes apoptosis distinct from
another form of cell death called necrosis in which uncontrolled cell death leads to lysis of
cells, inflammatory responses and, potentially, to serious health problems. Apoptosis, by
contrast, is a process in which cells play an active role in their own death (which is why
apoptosis is often referred to as cell suicide).

Upon receiving specific signals instructing the cells to undergo apoptosis a number of
distinctive changes occur in the cell. A family of proteins known as caspases are typically
activated in the early stages of apoptosis. These proteins breakdown or cleave key cellular
components that are required for normal cellular function including structural proteins in the
cytoskeleton and nuclear proteins such as DNA repair enzymes. The caspases can also
activate other degradative enzymes such as DNases, which begin to cleave the DNA in the
nucleus.
 Gene Control Eukaryotes
1. Chromatin Structure: The physical structure of the DNA, as it exists compacted into chromatin, can affect the
ability of transcriptional regulatory proteins (termed transcription factors) and RNA polymerases to find access to
specific genes and to activate transcription from them. The presence modifications of the histones and of CpG
methylation most affect accessibility of the chromatin to RNA polymerases and transcription factors.

2. Epigenetic Control: Epigenesis refers to changes in the pattern of gene expression that are not due to
changes in the nucleotide composition of the genome. Literally "epi" means "on" thus, epigenetics means "on"
the gene as opposed to "by" the gene.

3. Transcriptional Initiation: This is the most important mode for control of eukaryotic gene expression (see
below for more details). Specific factors that exert control include the strength of promoter elements within the
DNA sequences of a given gene, the presence or absence of enhancer sequences (which enhance the activity of
RNA polymerase at a given promoter by binding specific transcription factors), and the interaction between
multiple activator proteins and inhibitor proteins.
4. Transcript Processing and Modification: Eukaryotic mRNAs must be capped and polyadenylated, and the
introns must be accurately removed (see RNA Synthesis Page). Several genes have been identified that undergo
tissue-specific patterns of alternative splicing, which generate biologically different proteins from the same gene.

5. RNA Transport: A fully processed mRNA must leave the nucleus in order to be translated into protein.

6. Transcript Stability: Unlike prokaryotic mRNAs, whose half-lives are all in the range of 1 to 5 minutes,
eukaryotic mRNAs can vary greatly in their stability. Certain unstable transcripts have sequences (predominately,
but not exclusively, in the 3'-non-translated regions) that are signals for rapid degradation.
7. Translational Initiation: Since many mRNAs have multiple methionine codons, the ability of ribosomes to
recognize and initiate synthesis from the correct AUG codon can affect the expression of a gene product. Several
examples have emerged demonstrating that some eukaryotic proteins initiate at non-AUG codons. This
phenomenon has been known to occur in E. coli for quite some time, but only recently has it been observed in
eukaryotic mRNAs.

8. Small RNAs and Control of Transcript Levels: Within the past several years a new model of gene regulation
has emerged that involves control exerted by small non-coding RNAs. This small RNA-mediated control can be
exerted either at the level of the translatability of the mRNA, the stability of the mRNA or via changes in
chromatin structure.

9. Post-Translational Modification: Common modifications include glycosylation, acetylation, fatty acylation,

disulfide bond formations, etc.

10. Protein Transport: In order for proteins to be biologically active following translation and processing, they
must be transported to their site of action.

11. Control of Protein Stability: Many proteins are rapidly degraded, whereas others are highly stable. Specific
amino acid sequences in some proteins have been shown to bring about rapid degradation
 Gene Control Prokaryotes
1. Chromatin Structure: The physical structure of the DNA, as it exists compacted into
chromatin, can affect the ability of transcriptional regulatory proteins (termed
transcription factors) and RNA polymerases to find access to specific genes and to activate
transcription from them. The presence modifications of the histones and of CpG
methylation most affect accessibility of the chromatin to RNA polymerases and
transcription factors.
2. Epigenetic Control: Epigenesis refers to changes in the pattern of gene expression that
are not due to changes in the nucleotide composition of the genome. Literally "epi"
means "on" thus, epigenetics means "on" the gene as opposed to "by" the gene.
3. Transcriptional Initiation: This is the most important mode for control of eukaryotic
gene expression (see below for more details). Specific factors that exert control include
the strength of promoter elements within the DNA sequences of a given gene, the
presence or absence of enhancer sequences (which enhance the activity of RNA
polymerase at a given promoter by binding specific transcription factors), and the
interaction between multiple activator proteins and inhibitor proteins.
4. Transcript Processing and Modification: Eukaryotic mRNAs must be capped and
polyadenylated, and the introns must be accurately removed (see RNA Synthesis Page).
Several genes have been identified that undergo tissue-specific patterns of alternative
splicing, which generate biologically different proteins from the same gene.
5. RNA Transport: A fully processed mRNA must leave the nucleus in order to be
translated into protein.
6. Transcript Stability: Unlike prokaryotic mRNAs, whose half-lives are all in the range of 1 to
5 minutes, eukaryotic mRNAs can vary greatly in their stability. Certain unstable transcripts
have sequences (predominately, but not exclusively, in the 3'-non-translated regions) that are
signals for rapid degradation.
7. Translational Initiation: Since many mRNAs have multiple methionine codons, the ability of
ribosomes to recognize and initiate synthesis from the correct AUG codon can affect the
expression of a gene product. Several examples have emerged demonstrating that some
eukaryotic proteins initiate at non-AUG codons. This phenomenon has been known to occur
in E. coli for quite some time, but only recently has it been observed in eukaryotic mRNAs.
8. Small RNAs and Control of Transcript Levels: Within the past several years a new model of
gene regulation has emerged that involves control exerted by small non-coding RNAs. This
small RNA-mediated control can be exerted either at the level of the translatability of the
mRNA, the stability of the mRNA or via changes in chromatin structure.
9. Post-Translational Modification: Common modifications include glycosylation, acetylation,
fatty acylation, disulfide bond formations, etc.
10. Protein Transport: In order for proteins to be biologically active following translation and
processing, they must be transported to their site of action.
11. Control of Protein Stability: Many proteins are rapidly degraded, whereas others are
highly stable. Specific amino acid sequences in some proteins have been shown to bring
about rapid degradation.
Regulation of the lac operon in E. coli. The repressor of the operon is synthesized from the i gene.
The repressor protein binds to the operator region of the operon and prevents RNA polymerase
from transcribing the operon. In the presence of an inducer (such as the natural inducer,
allolactose) the repressor is inactivated by interaction with the inducer. This allows RNA
polymerase access to the operon and transcription proceeds. The resultant mRNA encodes the β-
galactosidase, permease and transacetylase activities necessary for utilization of β-galactosides
(such as lactose) as an energy source. The lac operon is additionally regulated through binding of
the cAMP-receptor protein, CRP (also termed the catabolite activator protein, CAP) to sequences
near the promoter domain of the operon. The result is a 50 fold enhancement of polymerase
activity.
http://themedicalbiochemistrypage.or
g/gene-regulation.html