Histones replication-independent incorporation

One possible function for H3.3 and some of the other replacement variants is to maintain the integrity of chromatin structure by replacing histones that are damaged or lost during normal cellular metabolism. Ahmad and Henikoff [104] suggested that replication independent incorporation of H3.3 could provide a mechanism to switch patterns of histone modification by removing H3 molecules that may be irreversibly modified by methylation. They also suggested that H3.3 could serve as a mark of transcriptionally active chromatin. One complication for... 

While some histone variants can become deposited during DNA replication, certain variants also are assembled into chromatin in a replication-independent manner (reviewed in Jin et al. 2005). This allows the incorporation of histone variant into chromosomal regions with high levels of histone turnover. Histone variants can distinguish the affected nucleosomes from their canonical counterparts and are likely to have important function in the specialization of chromatin domains and their epigenetic maintenance. 

While the synthesis of histones increases dramatically during DNA replication (see Ref. [99]), some variants are synthesized and incorporated into chromatin in absence of replication [100] these have been referred to as replication independent, basal, or replacement variants. Some variants show a mixed pattern with increased synthesis during replication, but continued expression in non-dividing cells (see Ref. [3], pp. 103-109). Several of the variants discussed above can be considered specialized replacement variants, including CENP-A [22], H2A.Z [35,100], H2A.X [56,100], and probably macroH2A. This section focuses on H3.3, an H3 replacement variant found in animals. 

Except for histone H4, each of the other histone types are found in different isoforms and are called histone variants. The chapter by Pehrson (Chapter 8) will provide a more in-depth discussion of these forms. It is worth pointing out that with regard to transcription through nucleosomes, some of these variants are expressed in a replication-independent process and are found in active gene fractions that have been prepared using the nuclease-sensitive solubilization procedures described above. Of particular note are two minor histone variants, H2A.Z and H3.3. Both are expressed throughout the cell cycle and incorporated into the nucleosomes of active genes ([38,39], see reviews [46,47]). For example, both Tetrahymena, H2A.Z (termed Tetrahymena hvl) and an H3.3-like histone (hv2) are preferentially present in the active macronucleus and are expressed in the micronucleus just prior to the time when this nucleus becomes transcriptionally active [48,49]. Suto et al. [50] have determined the crystal structure of a nucleosome... 

Variants of histone H2A are most common in higher eukaryotes. Thus far, five H2A-type histones have been described, of which two are found in all eukaryotes from yeast to mammals (Table 1). These are the histones H2A.X, and H2A.Z (Thatcher and Gorovsky 1994). While all other eukaryotes possess a canonical H2A, S. cerevisiae utilizes H2A.X as general, replication-dependent H2A form. Vertebrates possess an additional H2A variant named macroH2A, while the fifth known H2A variant H2ABBd (Barr body-deficient), is only conserved for mammals (Chow and Brown 2003 Gautier et al. 2004). Besides the most abundant canonical H2A, which is deposited into chromatin during DNA synthesis, other H2A variants also are synthesized outside of the S phase. Like specialized variants of H3, these proteins also are available for incorporation into chromatin independent of DNA replication. 

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