Chapter 18 (2)

True or False
All organisms must regulate which genes are expressed at any given time. They must continually turn genes on and off in response to signals from their external and internal environments.

Regulation of gene expression is also essential for cell __in multicellular organisms, which are made up of different types of cells, each with a distinct role.
True False

True or False:
To perform its role, each cell type must maintain a specific program of gene expression in which certain genes are expressed and others are not.
True False

A typical human cell probably expresses about __ of its genes at any given time. Highly differentiated cells (muscle/nerve) express smaller amounts.
Almost all the cells in an organism contain an identical __, except cells of the immune system.

True or False:
However, the subset of genes expressed in the cells of each type is unique, allowing these cells to carry out their specific function.

The differences between cell types are not due to different genes being present, but to ____, the expression of different genes by cells with the same genome.
True False

Only a small amount of DNA codes for __. The rest of the DNA either codes for RNA products or isn’t transcribed at all.
The __of a cell must locate the right genes at the right time.

When __goes awry, serious imbalances and diseases, including cancer, can arise.
In all organisms, a common __ for gene expression is at transcription; regulation at this stage is often in response to signals coming from outside the cell, like hormones or signal molecules.

For that reason, the term __ is often equated with transcription for both bacteria and eukaryotes.
· While this is most often the case for bacteria, the greater complexity of eukaryotic cell structure and function provides opportunities for regulating __ at many additional stages.

The basic unit of chromatin is the __. The structural organization of chromatin not only packs a cell’s DNA into a compact form that fits inside the nucleus but also helps regulate gene expression in several ways.

The location of a gene’s promoter relative to __and to the sites where the DNA attaches to the chromosome __or __can affect whether the gene is transcribed.

In addition, genes w/in __, which is highly condensed, are usually not expressed. The repressive effect of __has been seen in experiments in which a transcriptionally active gene was inserted into a region of __ in yeast cells; the inserted gene was no longer expressed.

Lastly, certain chemical modifications to the __and DNA of chromatin can influence both chromatin structure and gene expression.

__: Chemical modifications to histones, the proteins around which the DNA is wrapped in nucleosomes play a direct role in the regulation of gene transcription.

The __of each histone molecule in a nucleosome protrudes outward from the nucleosome. These __are accessible to various modifying enzymes, which catalyze the addition or removal of specific chemical groups.

In __, __groups (-COCH3) are attached to __in histone tails; __is the removal of acetyl groups. When the lysines are acetylated, their positive charges are neutralized and the histone tails no longer bind to neighboring nucleosomes.

Such binding promotes the folding of __into a more compact structure; when this binding does not occur, chromatin has a looser structure.
§ As a result, transcription proteins have easier access to genes in an __region.

Some enzymes that __ or __ histones are closely associated with or even components of the transcription factors that bind to promoters. These observations suggest that __ may promote the initiation of transcription not only by remodeling chromatin structure, but also by binding to and thus “__” components of the transcription machinery.

Several other chemical groups can be reversibly attached to amino acids in histone tails- e.g. __ and __
§ The addition of __groups (-CH3) to histone tails (__) can promote condensation of the chromatin.

The addition of __groups to amino acids (__) next to a methylated amino acid can have the opposite effect.

__: those and many mother modifications to histone tails affect chromatin structure and gene expression. It proposes that specific combinations of modifications, rather than the overall level of histone acetylation, help determine the chromatin configuration, which in turn influences transcription.

__: A different set of enzymes can methylate certain bases in the DNA itself. (Inactive mammalian X chromosomes) They are generally more methylated than DNA that is actively transcribed, although there are no exceptions.

Some genes are more heavily __in cells in which they’re not expressed. Removal of the extra __groups can turn on some of these genes. There are some proteins that bind to __DNA and recruit __.

Thus, a dual mechanism, involving both __and __, can repress transcription.
o In some species, __seems to be essential for the long-term inactivation of genes that occurs during normal cell differentiation in the embryo.
o Once __, genes usually stay that way through successive cell divisions.

At DNA sites where one strand is already methylated, __correctly methylate the daughter strand after each round of DNA replication.

__patterns are thus passed on, and cells forming specialized tissues keep a chemical record of what occurred during __.

A __pattern maintained in this way also accounts for __, where methylation permanently regulates expression of either the maternal or paternal allele of particular genes at the start of development.

Inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence is called __.
Whereas mutations in the DNA are permanent, modifications to the __can be reversed, by processes that are not yet fully understood.
The molecular systems for chromatin modification may well interact with each other in a regulated way.

Alterations in normal patterns of DNA __are seen in some cancers, were they are associated with inappropriate gene expression
Evidently, enzymes that modify __structure are integral parts of the eukaryotic cell’s machinery for regulating transcription.
__provide initial control of gene expression by making a region of DNA either more or less able to bind the transcription machinery.

Once the chromatin is modified for expression, the __ is next in regulation.
In bacteria and eukaryotes, the regulation of __in eukaryotes involves proteins that bind to DNA and either facilitate or inhibit binding of RNA pol.
A cluster of proteins called a __assembles on the promoter sequence at the upstream end of the gene. One protein, __, then transcribes the gene, making a primary RNA transcript.

Associated with most eukaryotic genes are multiple __, segments of noncoding DNA that help regulate transcription by binding certain proteins.
· These __ and the proteins they bind are critical to the precise regulation of gene expression seen in different cell types.

For transcription, euk RNA pol needs help from __.
· Some transcription factors are essential for the transcription of all protein-coding genes; therefore, they are often called __.
· Only a few general __ independently bind a DNA sequence, like the TATA box; the others bind proteins, including each other and RNA pol II.
· Only when the complete __is assembled can the pol begin to produce a complementary strand of RNA.

The interaction of __ and RNA pol II with a promoter usually leads to only a low rate of initiation and production of few RNA transcripts.
· In euk, high levels of transcription of particular genes at the appropriate time and place depend on interaction of __with another set of proteins, which can be thought of as __.

Control elements located close to the promoter are __,
The more distant__, groupings of which are enhancers, may be thousands of nucleotides upstream or downstream of a gene or even within an intron.

A given gene may have multiple __, each active at a different time or in a dif cell type or location in the organism.
· Each __is associated with only that gene and no other.
In euk, the rate of gene expression can be strongly increased or decreased by the binding of proteins, either activators or repressors, to the __ of __.

__of the DNA is thought to bring the bound activators in contact with a group of so-called __, which in turn interact with proteins at the promoter.
· These multiple protein-protein interaction help assemble and position the initiation complex on the promoter.

Hundreds of transcription activators have been discovered in euk. Researchers have identified two common structural elements in a large number of activator proteins: a __- a part of the protein’s 3D structure that binds to DNA- and one or more __.

__bind other regulatory proteins or components of the transcription machinery, facilitating a sequence of protein-protein interactions that results in transcription of a given gene.

Specific transcription factors that function as repressors can inhibit gene expression in several different ways.
· Some bind directly to the __DNA (in __or elsewhere), blocking activator binding or, in some cases, turning off transcription even when activators are bound.
· Others block the binding of activators to proteins that allow the activators to bind to DNA.

In addition to influencing transcription directly, some activators and repressors act indirectly by affecting chromatin structure.
· Some activators recruit proteins that __histones near the promoters of specific genes, thus promoting __.
· Similarly, some recruit proteins that __histones, leading to reduced transcription, called __. Indeed, recruitment of chromatin-modifying proteins seems to be the most common mechanism of repression in euk.

In euk, the precise control of transcription depends largely on the binding of __to DNA __. (The number of completely different nucleotide sequences found in control elements is small. A dozen or so short nucleotide sequences appear again and again in the __for different genes.
On avg., each __is composed of about 10 __, each of which can bind only one or two specific transcription factors.

The particular combination of __ in an __associated with a gene turns out to be more important than the presence of a single unique __in regulating transcription of the gene.
Even with only a dozen __sequences available, a very large number of combos are possible.

A particular combination of __ will be able to activate transcription only when the appropriate activator proteins are present, which may occur at a precise time during development or in a particular cell type.
Genes are expressed together, and the encoded proteins are produced concurrently.

Analysis of the genomes of several eukaryotic species has revealed some __that are clustered ear one another on the same chromosome.
Unlike genes of bacterial operons, each gene in such a cluster has its own promoter and is individually transcribed.

The coordinate regulation of these __genes is thought to involve changes in chromatin structure that make the entire group of genes either available or unavailable for transcription.
In other cases, including __ of nematode genes, several related genes do share a promoter and are transcribed into a __.

__eukaryotic genes are found scattered over different chromosomes. In these cases, __seems to depend on the association of a specific combination of control elements with every gene of a dispersed group.
Copies of the activators that recognize control elements bind to them, promoting simultaneous transcription of the genes, no matter where they are in the genome.

__ of dispersed genes in a euk cell often occurs in response to chemical signals from outside the cell.
Many signal molecules bind to receptor on a cell’s surface and never actually enter the cell. Such molecules can control gene expression indirectly by triggering __that lead to activation of particular transcription activators or repressors.

The principle of __is the same as in the case of steroid hormones: Genes with the same control elements are activated by the same chemical signals. Systems for coordinating gene regulation probably arose early in evolutionary history.
The expression of a protein-coding gene is ultimately measured by the amt of functional protein a cell makes, and much happens between the synthesis of the __and the activity of the protein in the cell.

__contains __, in which different mRNA molecules are produced from eh same primary transcript, depending on which RNA segments are treated as exons and which as introns.
Regulatory proteins specific to a cell type control intron-exon choices by binding to regulatory sequences within the primary transcript.

The life span of __molecules in the cytoplasm is important in determining the pattern of protein synthesis in a cell.
· __is degraded by enzymes w/in a few minutes of their synthesis.
o This short life span of mRNAs is one reason bacteria can change their patterns of protein synthesis so quickly In response to environmental changes.
· __ usually survive for hrs, days or weeks.

A common pathway of mRNA breakdown begins with the enzymatic shortening of the __. This helps trigger the action of enzymes that remove the __.
Removal of the __, a critical step, is also regulated by particular nucleotide sequences w/in the mRNA.
Once the cap is removed, __enzymes rapidly chew up the mRNA.

Nucleotide sequences that affect how long an mRNA remains intact are often found in the __.

__ presents another opportunity for regulating gene expression: such regulation occurs most commonly at the __stage.
The __of some mRNAs can be blocked by regulatory proteins that bind to specific sequences or structures within the __at the __’ end of the mRNA, preventing the attachment of __.

A different mechanism for blocking translation is seen in a variety of mRNAs present in the eggs of many organisms: Initially, these stored mRNAs lack __of sufficient length to allow __.
At the appropriate time during embryonic development, a __ adds more A nucleotides, prompting translation to begin.

Alternatively, __of all the mRNAs in a cell may be regulated simultaneously.
In a euk cell, such “global” control usually involves the activation or inactivation of one or more of the __required to initiate translation.
o This mechanism plays a role in starting __of mRNAs that are stored in eggs. Just after fertilization, translation is triggered by the sudden activation of __. The response is a burst of synthesis of proteins encoded by the stored mRNAs.

The final opportunity for controlling gene expression is after __.
Often, euk polypeptides must be processed to yield functional protein molecules.
In addition, many proteins undergo __that make them functional. Regulatory proteins are commonly activated or inactivated by the reversible addition of __groups, and proteins destined for the surface of animal cells acquire __.

__and many others must also be transported to target destinations in the cell in order to function. Regulation might occur at any of the steps involved in modifying or transporting a protein.

Finally, the length of time each protein functions in the cell is strictly regulated by mean of __. Many proteins, like __, must be relatively short-lived if the cell is to function appropriately.

To mark a particular protein for destruction, the cell commonly attaches molecules of a small protein called __to the protein.
Giant protein complexes called __then recognize the __-tagged proteins and degrade them.