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Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

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AN OVERVIEW OF GENE CONTROL

371

no. of

reads

(A)

no. of

reads

(B)

start of transcription

exons

exons

β-actin gene

tyrosine aminotransferase gene

introns

introns

CELL LINE

embryonic stem cell

liver cell

muscle cell

blood vessel cell

blood cell precursor

skin cell

lung cell

CELL LINE

embryonic stem cell

liver cell

muscle cell

blood vessel cell

blood cell precursor

skin cell

lung cell

still do not have an exact answer to this fundamental question, we can make several

general statements.

1. Many processes are common to all cells, and any two cells in a single

organism therefore have many gene products in common. These include

the structural proteins of chromosomes, RNA and DNA polymerases, DNA

repair enzymes, ribosomal proteins and RNAs, the enzymes that catalyze

the central reactions of metabolism, and many of the proteins that form the

cytoskeleton such as actin (Figure 7–3A).

2. Some RNAs and proteins are abundant in the specialized cells in which

they function and cannot be detected elsewhere, even by sensitive tests.

Hemoglobin, for example, is expressed specifically in red blood cells,

where it carries oxygen, and the enzyme tyrosine aminotransferase (which

breaks down tyrosine in MBoC6 food) n7.200/7.03

is expressed in liver but not in most other

tissues (Figure 7–3B).

3. Studies of the number of different RNAs suggest that, at any one time, a

typical human cell expresses 30–60% of its approximately 30,000 genes at

some level. There are about 21,000 protein-coding genes and a roughly estimated

9000 noncoding RNA genes in humans. When the patterns of RNA

expression in different human cell lines are compared, the level of expression

of almost every gene is found to vary from one cell type to another. A

few of these differences are striking, like those of hemoglobin and tyrosine

aminotransferase noted above, but most are much more subtle. But even

those genes that are expressed in all cell types usually vary in their level of

expression from one cell type to the next.

4. Although there are striking differences in coding RNAs (mRNAs) in specialized

cell types, they underestimate the full range of differences in the final

pattern of protein production. As we discuss in this chapter, there are many

steps after RNA production at which gene expression can be regulated.

And, as we saw in Chapter 3, proteins are often covalently modified after

they are synthesized. The radical differences in gene expression between

cell types are therefore most fully revealed through methods that directly

display the levels of proteins along with their post-translational modifications

(Figure 7–4).

Figure 7–3 Differences in RNA levels

for two human genes in seven different

tissues. To obtain the RNA data by the

technique known as RNA-seq (see

p. 447), RNA was collected from human

cell lines grown in culture, derived from

each of the seven indicated tissues. Millions

of “sequence reads” were obtained and

mapped across the human genome by

matching RNA sequences to the DNA

sequence of the genome. At each position

along the genome, the height of the colored

trace is proportional to the number of

sequence reads that match the genome

sequence at that point. As seen in the

figure, the exon sequences in transcribed

genes are present at high levels, reflecting

their presence in mature mRNAs. Intron

sequences are present at much lower

levels and reflect pre-mRNA molecules

that have not yet been spliced plus intron

sequences that have been spliced out but

not yet degraded. (A) The gene coding for

“all-purpose” actin, a major component

of the cytoskeleton. Note that the lefthand

end of the mature β-actin mRNA is

not translated into protein. As explained

later in this chapter, many mRNAs have

5ʹ untranslated regions that regulate their

translation into protein. (B) The same type

of data displayed for the enzyme tyrosine

aminotransferase, which is highly expressed

in liver cells but not in the other cell types

tested. (Information for both panels from the

University of California, Santa Cruz, Genome

Browser (http://genome.ucsc.edu), which

provides this type of information for every

human gene. See also S. Djebali et al.,

Nature 489:101–108, 2012.)

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