Some Regions Of Chromatin Are Active Others Are Inactive

Generally, every cell of an individual metazoan organism contains the same genetic information. Thus, the differences between cell types within an organism must be explained by differential expression of the common genetic information. Chromatin containing active genes (ie, transcriptionally active chromatin) has been shown to differ in several ways from that of inactive regions. The nucleosome structure of active chromatin appears to be altered, sometimes quite extensively, in highly active regions. DNA in active chromatin contains large regions (about 100,000 bases long) that are sensitive to diges tion by a nuclease such as DNase I. DNase I makes single-strand cuts in any segment of DNA (no sequence specificity). It will digest DNA not protected by protein into its component deoxynucleotides. The sensitivity to DNase I of chromatin regions being actively transcribed reflects only a potential for transcription rather than transcription itself and in several systems can be correlated with a relative lack of 5-methyldeoxycytidine in the DNA and particular histone covalent modifications (phosphorylation, acetylation, etc; see Table 36-1).

Within the large regions of active chromatin there exist shorter stretches of 100-300 nucleotides that exhibit an even greater (another tenfold) sensitivity to DNase I. These hypersensitive sites probably result from a structural conformation that favors access of the nuclease to the DNA. These regions are often located immediately upstream from the active gene and are the location of interrupted nucleosomal structure caused by the binding of nonhistone regulatory transcription factor proteins. (See Chapters 37 and 39.) In many cases, it seems that if a gene is capable of being transcribed, it very often has a DNase-hypersensitive site(s) in the chro-matin immediately upstream. As noted above, nonhis-tone regulatory proteins involved in transcription control and those involved in maintaining access to the template strand lead to the formation of hypersensitive sites. Hypersensitive sites often provide the first clue about the presence and location of a transcription control element.

Transcriptionally inactive chromatin is densely packed during interphase as observed by electron microscopic studies and is referred to as heterochro-matin; transcriptionally active chromatin stains less densely and is referred to as euchromatin. Generally, euchromatin is replicated earlier than heterochromatin in the mammalian cell cycle (see below).

There are two types of heterochromatin: constitutive and facultative. Constitutive heterochromatin is always condensed and thus inactive. It is found in the regions near the chromosomal centromere and at chromosomal ends (telomeres). Facultative heterochro-matin is at times condensed, but at other times it is actively transcribed and, thus, uncondensed and appears as euchromatin. Of the two members of the X chromosome pair in mammalian females, one X chromosome is almost completely inactive transcriptionally and is hete-rochromatic. However, the heterochromatic X chromosome decondenses during gametogenesis and becomes transcriptionally active during early embryogenesis— thus, it is facultative heterochromatin.

Certain cells of insects, eg, Chironomus, contain giant chromosomes that have been replicated for ten cycles without separation of daughter chromatids. These copies of DNA line up side by side in precise register and produce a banded chromosome containing regions of condensed chromatin and lighter bands of

Metaphase chromosome

Metaphase chromosome

Condensed loops

Non-condensed loops

Nuclear-scaffold associated form

Nuclear-scaffold associated form

700 nm

Chromosome scaffold m

30-nm chromatin fibril composed of nucleosomes

"Beads-

on-a-string"

10-nm chromatin fibril

Naked double-helical DNA

Chromosome scaffold

30-nm chromatin fibril composed of nucleosomes

"Beads-

on-a-string"

10-nm chromatin fibril

30 nm 1

10 nm

Figure 36-3. Shown is the extent of DNA packaging in metaphase chromosomes (top) to noted duplex DNA (bottom). Chromosomal DNA is packaged and organized at several levels as shown (see Table 36-2). Each phase of condensation or compaction and organization (bottom to top) decreases overall DNA accessibility to an extent that the DNA sequences in metaphase chromosomes are almost totally transcriptionally inert. In toto, these five levels of DNA compaction result in nearly a 104-fold linear decrease in end-to-end DNA length. Complete condensation and decondensation of the linear DNA in chromosomes occur in the space of hours during the normal replicative cell cycle (see Figure 36-20).

30 nm 1

10 nm

'WWV

Figure 36-3. Shown is the extent of DNA packaging in metaphase chromosomes (top) to noted duplex DNA (bottom). Chromosomal DNA is packaged and organized at several levels as shown (see Table 36-2). Each phase of condensation or compaction and organization (bottom to top) decreases overall DNA accessibility to an extent that the DNA sequences in metaphase chromosomes are almost totally transcriptionally inert. In toto, these five levels of DNA compaction result in nearly a 104-fold linear decrease in end-to-end DNA length. Complete condensation and decondensation of the linear DNA in chromosomes occur in the space of hours during the normal replicative cell cycle (see Figure 36-20).

more extended chromatin. Transcriptionally active regions of these polytene chromosomes are especially decondensed into "puffs" that can be shown to contain the enzymes responsible for transcription and to be the sites of RNA synthesis (Figure 36-4).

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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