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replication

old H3-H4 tetramer acetyl transferase binds aoetylated histone tails replication

old H3-H4 tetramer old H3-H4 tetramer acetyl transferase binds aoetylated histone tails

FIGURE 7-42 Inheritance of parental H3-H4 tetramers facilitates the inheritance of chromatin states. As a chromosome is replicated, the distribution of the parental H3-H4 tetramers results in the daughter chromosomes receiving the same modifications as the parent. The ability of these modifications to recuit enzymes that perform the same modifications facilitates the correct propagation of the same state of modification to the two daughter chromosomes. Acetylatmn is shown on the core regions of the histones for simplicity. In reality, this modification is generally on the N terminal tails.

acetyl transferase

Dendritic Cell Mhci

modification of adjacent "new" histones acetyl transferase modification of adjacent "new" histones

resulted in little or no nueleosome formation. Instead, the majority of the histnnes aggregate in a nonproductive form. For correct nucleo-some assembly, it was necessary to raise salt concentrations to very high levels (>1 M NaCl) and then slowly reduce the concentration over many hours. Although useful for assembling nucleosomes for in vitro studies (such as for the structural studies of the nueleosome described earlier), elevated salt concentrations are not involved in nueleosome assembly in vivo.

Studies of nueleosome assembly under physiological salt concentrations identified factors required to direct the assembly of hi stones onto the DNA. These factors are negatively-charged proteins that form complexes with either H3*H4 tetramers or H2A-II2B dinners (see Table 7-8) and escort them to sites of nueleosome assembly. Because they act to keep histories from interacting with the DNA nonpreductive ly, these factors have been referred to as histone chaperones (see Figure 7-43).

How do the histone chaperones direct nueleosome assembly to sites of new DNA synthesis? Studies of the histone H3*f 14 tetramer chaperone OAF-1 reveal a likely answer. Nueleosome assembly directed by CAF-I requires that the target DNA is replicating. Thus, replicating DNA is marked in some way for nueleosome assembly. Interestingly, this mark is gradually lost after replication is completed. Studies of CAF-Fdependent assembly have determined that the mark is a ring-shaped sliding clamp protein called PCNA, As we will discuss in detail in Chapter 8, this factor forms a ring around the DNA duplex and is responsible for holding DNA polymerase on the DNA during DNA synthesis, Afttir the polymeria« is finished, PCNA is released from the DNA polymerase but is still linked to the DNA. In this condition, PCNA is available to interact with other proteins. CAF-I associates with the released PtTNA and assembles H3-H4 tetramers preferentially on the PCNA-bound DNA. Thus, by associating with e component of the DNA replication machinery, CAF-1 is directed to assemble nucleosomes at sites of recent DNA replication.

old histories: H2A ■ H2B ■ H3 ■ H4 new histones: £ H2A □ H2B □ H3 [J H4

old histories: H2A ■ H2B ■ H3 ■ H4 new histones: £ H2A □ H2B □ H3 [J H4

H2A-H2B ifimer

FIGURE 7-43 Chromatin assembly factors facilitate the assembly of nucleosomes After the replication fork has passed, chromatin assembly factors chaperone free H3-H4 tetramers (CAT-I) and H2A-H2B dimers (NAP-I) to the site of newly replicated DNA. Once at the newly replicated DNA, these factors transfer their histone contents to ttie DNA. The CAM factors aie recruited to the newly replicated DNA by interactions with ONA sliding damps. These nng-shaped, auxiliary replf cation factors encinde the DNA and are released from the replication machinery as the replication fork moves. A more detailed description of DNA sliding clamps and their function in DNA replication is presented in Oiapter 8.

TABLE 7-8 Properties of His tone Chape rone s

Number of Hi stones Interaction with

Name subunits bound sliding clamp

OAF-I 4 H3-H4 Yes

RCAF 1 H3-H4 No

NAP-J 1 R5A-H2B No

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