CH 18 Regulation of Gene Expression

(18.1) Bacteria often respond to environmental change by regulating transcription
A cell can regulate the production of enzymes by __ or __

feedback inhibition or gene regulation
(Feedback inhibition= The activity of the first enzyme in the pathway is inhibited by the pathway's end product�tryptophan. Thus, if tryptophan accumulates in a cell, it shuts down the synthesis of more tryptophan by

One mechanism for control of gene expression in bacteria is the ___

operon model

A key advantage of grouping genes of related function into one transcription unit is that a single ___ can control the whole cluster of functionally related genes; in other words, these genes are coordinately controlled
The switch is a segment of DNA call

on-off switch"
operator

An __ is the entire stretch of DNA that includes the operator, the promoter, and the genes that they control

operon

The operon can be switched off by a protein ___

repressor

The repressor is the product of a separate ___, located some distance from the operon itself

regulatory gene

A __ is a molecule that cooperates with a repressor protein to switch an operon off

corepressor

By default, the trp operon is on and the genes from ___ are transcribed

tryptophan synthesis

When __ is present, it binds to the trp repressor protein, which turns the operon off

tryptophan

The repressor is active only in the presence of its ___; thus the trp operon is turned off (repressed) if __ levels are high

corepressor tryptophan
tryptophan

A repressible (limit) operon is 1 that is usually on; binding of a repressor to the operator shuts off ___

transcription

The trp operon is a ____

repressible operon

An ___ is 1 that is usually off; a molecule called an inducer inactivates the repressor and turns on transcription

inducible operon

The __ is an inducible operon and contains genes that code for enzymes used in the hydrolysis and metabolism of lactose

lac operon

By itself, the lac repressor is ___ and switches the lac operon __

active
off

A molecule called an ___ inactivates the repressor to turn the lac operon on

inducer

Which 3 enzymes help breakdown lactose?

B-galctosidase
Permease
Transacetylase

___ usually function in catabolic pathways; their synthesis is induced by a chemical signal, which is allolactose

Inducible enzymes

The enzymes for tryptophan synthesis are said to be repressible.
__ usually function in anabolic pathways; their synthesis is repressed by high levels of the end product (tryptophan)

Repressible enzymes

Regulation of both the trp and lac operons involves __ of genes because operons are switched off by the active form of the repressor

negative control

18.2 Eukaryotic gene expression is regulated at many stages
All organisms, whether prokaryotes or eukaryotes, must regulate which genes are expressed at any given time. Both unicellular organisms and the cells of multicellular organisms continually turn _

Genes
gene expression

Differences between cell types are not from different genes being present but result from ___, the expression of different genes by cells with the same genome

differential gene expression

Regulation of Chromatin Structure
Genes with highly packed heterochromatin are usually ___

not expressed

Chemical modifications to chromatin--- both to the histone proteins of the nucleosomes around which DNA is wrapped and to the nucleotides that make up that DNA---- can influence ___ and ___

chromatin structure and gene expression

Histone Modifications and DNA Methylation
In ___, acetyl groups are attached to an amino acid in a histone tail
This appears to open up the chromatin structure, thereby promoting the ___

histone acetylation
initiation of transcription

The addition of ___ can condense chromatin and reduce transcription

methyl groups (methylation)

___ can cause long-term inactivation of genes in cellular differentiation

DNA methylation

In ___, methylation regulates expression of either the maternal or parental alleles of certain genes at the start of development

genomic imprinting

The inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequences is called ____
Whereas mutations in the DNA are permanent changes, modifications to the chromatin can be reversed.

epigenetic inheritance

Associated with most eukaryotic genes are multiple ___, segments of noncoding DNA that serve as binding sites for transcription factors that help regulate transcription

control elements

___ requires the assistance of transcription factors to initiate transcription

RNA polymerase

General transcription factors are essential for the transcription of all ___
A few bind to the __within the promoter. Many bind to proteins, including other transcription factors and ___

protein-coding genes
TATA box
RNA polymerase II

Only when the complete initiation complex has assembled can the __ begin to move along the template strand of the DNA
It produces a __

RNA polymerase
complementary strand of RNA

For genes that are not expressed all the time, high levels of transcription depend on the presence of another set of factors, ___. In eukaryotes, the rate of gene expression can be strongly increased or decreased by the binding of specific transcription f

specific transcription factors

__ are located close to the promoter
__, groupings of which are called enhancers, may be far away from a gene or even located in an intron

Proximal control elements
Distal control elements

Each __ is generally associated with only 1 gene and no other (specific)

enhancer

An ___, is a protein that binds to an enhancer and stimulates transcription of a gene

activator

Activators have 2 domains, 1 that binds ___ and a second that activates ___

DNA
transcription

A particular combination of control elements in an enhancer can activate transcription only when the appropriate ___ are present

activator proteins

Nuclear Architecture and Gene Expression
Chromosome confirmation capture techniques allow identification of regions of ___ that interact with each other during interphase

chromosomes

Different ___ from the same chromosomes or from other chromosomes may congregate at particular sites, some of which are rich in transcription factors and RNA polymerases

loops of chromatin

RNA Processing
In ___, different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which as introns

alternative RNAsplicing

Initiation of Translation and mRNA Degradation
The lifespan of ___ in the cytoplasm is important in determining the pattern of protein synthesis in a cell. Bacterial mRNA molecules typically are degraded by enzymes within a few minutes of their synthesis.

mRNA molecules

In contrast, __ mRNA is more long-lived than prokaryotic mRNA

Eukaryotic

Nucleotide sequences that influence the lifespan of mRNA in eukaryotes reside in the ___ at 3' end of the molecule

untranslated region (UTR)

Protein Processing and Degradation
The final opportunities for controlling gene expression occur after translation.
After translation, polypeptides undergo processing, including __ and chemical modifications

cleavage

Cells mark proteins for degradation by attaching __ to them.
This mark is recognized by __, which recognize and degrade the proteins

ubiquitin
proteasomes

A significant fraction of the genome may be transcribed into ___.

noncoding RNAs (ncRNAs)

What are two types of ncRNAs?

miRNA and siRNA

__ are small, single-stranded RNA molecules that can bind complementary sequences in mRNA

microRNAs (miRNAs)

The miRNAs and associated proteins cause __ of the target mRNA or sometimes block its translation

degradation

__ are similar to miRNAs in size and function

small interfering RNAs (siRNAs)

The blocking of gene expression by siRNAs is called __ and it is used in the laboratory as a means of disabling specific genes to investigate their function.

RNA interference (RNAi)

Small ncRNAs called ___ induce formation of heterochromatin, blocking the expression of parasitic DNA elements in the genome known as transposons

piwi-interacting RNAs (piRNAs)

piRNAs help to reestablish appropriate ___ during gamete formation in many animal species

methylation patterns

___ range from 200 to hundreds of thousands of nucleotides in length
1 type of lncRNA is responsible for ___, which, in most female mammals, prevents expression of genes located on one of the X chromosomes.
(Barr body)

Long noncoding RNAs (lncRNAs)
X chromsome inactivation

18.4: A program of differential gene expression leads to the different cell types in a multicellular organism
___ orchestrates the developmental programs of animals

Gene expression

During embryonic development, cells not only increase in number, but also undergo__, the process by which cells become specialized in the structure and function.
The different kinds of cells are not randomly distributed but are organized into tissues and

Cell differentiation

Almost all cells in an organism have the same genome; therefore, __ results from genes being regulated differently in each cell type

Differential gene expression

It turns out that materials placed into the ___ by maternal cells set up a sequential program of gene regulation that is carried out as embryonic cells divide, and this program coordinates cell differentiation during embryonic development.

egg

One important source of information early in development is the egg's cytoplasm, which contains both RNA and proteins encoded by the mother's DNA. The cytoplasm of an unfertilized egg is not homogeneous. Messenger RNA, proteins, other substances, and orga

cytoplasmic determinants

In the process called ___, signal molecules from embryonic cells cause changes in nearby target cells

induction

The genes Lewis discovered, called ___, are regulatory genes that control pattern formation in the late embryo, larva, and adult. (regulatory genes that control placement and spatial organization of body parts in animals, plants, and fungi by controlling

homeotic genes

__ can be caused by mutations to genes that normally regulate cell growth and division

Cancer

Mutations in these genes can be caused by __ or environmental influences such as chemicals, radiation, and some viruses

spontaneous mutation

__ are cancer-causing genes

oncogenes

__ are the corresponding normal cellular genes that are responsible for normal cell growth and division

proto-oncogenes

proto-oncogenes can be converted to oncogenes by:
1) movement of __ within the genome
(If a translocated protonate-oncogene ends up near an especially active promoter (or other control element), its transcription may increase, making it an oncogene)
2) am

1) DNA
2) proto-oncogene
3) point mutations

__ genes normally inhibit cell division

Tumor-suppressing genes

Tumor suppressing proteins:
1) ___ damaged DNA
(a function that prevents the cell from accumulating cancer-causing mutations)
2) Control cell __
(control the adhesion of cells to each other or to the extracellular matrix; proper cell anchorage is crucial

1) repair
2) adhesion (cling to each other)
3) inhibit

Mutations in the __ and __ are common in human cancers

ras-proto-oncogene and p53 tumor-suppressor gene

Mutations in the __ can lead to production of a hyperactive
Ras protein (a G-protein) and increased cell division

ras gene

Mutations in the __ prevent suppression of the cell cycle

p53 gene

If DNA is irreparable, __ activates cell "suicide" genes, whose protein products bring about programmed cell death

p53

At the DNA level, a cancerous cell is usually characterized by at least 1 __ and the mutation of several tumor-suppressor genes

active oncogene