Page 247 - Color Atlas of Biochemistry
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238 Molecular genetics
Genome The non-histone proteins are very hetero-
geneous. This group includes structural pro-
teins of the nucleus, as well as many enzymes
A. Chromatin
and transcription factors (see p. 118), which
In thenuclei ofeukaryotes (seep. 196), DNA is selectively bind to specific segments of DNA
closely associated with proteins and RNA. and regulate gene expression and other pro-
These nucleoprotein complexes, with a DNA cesses.
proportion of approximately one-third, are
known as chromatin.Itisonlyduringcell
division (see p. 394) that chromatin con- B. Histones
denses into chromosomes that are visible The histones are remarkable in several ways.
under light microscopy. During interphase, With their high proportions of lysine and ar-
most of the chromatin is loose, and in these ginine (blue shading), they are strongly basic,
conditions a morphological distinction can be as mentioned above. In addition, their amino
made between tightly packed heterochroma- acid sequence has hardly changed at all in the
tin and the less dense euchromatin.Euchro- course of evolution. This becomes clear when
matin is the site of active transcription. one compares the histone sequences in mam-
The proteins contained in chromatin are mals, plants, and fungi (yeasts are single-
classified as either histone or non-histone celled fungi; see p. 148). For example, the
proteins. Histones (B) are small, strongly basic H4 histones in humans and wheat differ
proteins that are directly associated with only in a single amino acid residue, and there
DNA. They contribute to the structural organ- are only a few changes between humans and
ization of chromatin, and their basic amino yeast. In addition, all of these changes are
acids also neutralize the negatively charged “conservative”—i. e., thesizeand polarity
phosphate groups, allowing the dense pack- barely differ. It can be concluded from this
ing of DNA in the nucleus. This makes it pos- that the histones were already “optimized”
siblefor the46DNA moleculesof the diploid when the last common predecessor of ani-
9
human genome, with their 5 10 base pairs mals, plants, and fungi was alive on Earth
(bp) and a total length of about 2 m, to be (more than 700 million years ago). Although
accommodated in a nucleus with a diameter countless mutations in histone genes have
of only 10 µm. Histones also play a central taken place since, almost all of these evidently
role in regulating transcription (see p. 244). led to the extinction of the organisms con-
Two histone molecules each of types H2A cerned.
(blue), H2B (green), H3 (yellow), and H4 (red) The histones in the octamer carry N-termi-
form an octameric complex, around which nal mobile “tails” consisting of some 20 amino
146 bp of DNA are wound in 1.8 turns. These acid residues that project out of the nucleo-
particles, with a diameter of 7 nm, are re- somes and are important in the regulation of
ferred to as nucleosomes. Another histone chromatin structure and in controlling gene
(H1) binds to DNA segments that are not di- expression (see A2; only two of the eight tails
rectly in contact with the histone octamers are shown in full length). For example, the
(“linker” DNA). It covers about 20 bp and sup- condensation of chromatin into chromo-
ports the formation of spirally wound super- somes is associated with phosphorylation (P)
structures with diameters of 30 nm, known as of the histones, while the transcription of
solenoids. When chromatin condenses into genes is initiated by acetylation (A) of lysine
chromosomes, the solenoids form loops about residues in the N-terminal region (see p. 244).
200 nm long, which already contain about
80 000 bp. The loops are bound to a protein
framework (the nuclear scaffolding), which in
turn organizes some 20 loops to form mini-
bands. A large number of stacked minibands
finally produces a chromosome. In the chro-
mosome, the DNA is so densely packed that
the smallest human chromosome already
contains more than 50 million bp.
Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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