Chromatin transcriptionally active

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

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... 

H3 replacement variants are also present in plants [108] and Tetrahymena [109]. Phylogenetic analyses indicates that these H3 replacement variants arose independently of animal H3.3 [109]. Like H3.3, the plant H3 replacement variant also appears to be preferentially deposited into transcriptionally active chromatin [110]. The H3 replacement variant in Tetrahymena, hv2, is found only in the transcriptionally active macronucleus [49]. In contrast to H3.3, the amino acid differences between hv2 and the replication dependent H3 of Tetrahymena do not appear to be essential for replication independent incorporation into chromatin [111]. In this case constitutive expression appears to be the dominant factor that can drive replication independent deposition of hv2 or an H3 variant that is normally replication dependent. This difference between hv2 and H3.3 is not necessarily surprising because hv2 appears to have arisen independently of H3.3 and does not have the structural features characteristic of H3.3 [109]. 

Messenger RNAs for H2A.Bbd have been detected in human testis, fibroblasts and lymphocytes [77], but little is known about the amount of H2A.Bbd protein in these or other human cell types or about its presence in other species. The distribution of H2A.Bbd in chromatin was examined by expressing epitope-tagged or GFP-tagged H2A.Bbd in cultured cells. These studies revealed a striking deficiency of H2A.Bbd in the inactive X chromosome, leading to its name which stands for Histone H2A Barr-body deficient [77]. The distribution of H2A.Bbd overlapped extensively with that of H4 acetylated on lysine 12, suggesting that H2A.Bbd may preferentially associate with transcriptionally active chromatin. 

Chromatin fractionation approaches including ChIP assays have provided evidence for and against uH2A and uH2B being associated with transcriptionally active chromatin [270,281-285]. Most evidence supports uH2A being associated... 

The association between a histone tail modification and a particular functional state of chromatin, came with the demonstration that transcriptionally active chromatin fractions were enriched in acetylated histones, firstly by biochemical co-fractionationation ([8,9] and references therein) and then by Chromatin ImmunoPrecipitation, ChIP [10]. Subsequently, regions of transcriptionally silent constitutive and facultative heterochromatin, were shown, by immunofluorescence microscopy, to be under-acetylated [11,12]. This supported the idea that acetylation of the histone tails, with the associated loss of positive charge and reduction in DNA-binding constant, somehow caused chromatin to become more open (or less condensed ) and thereby more conducive to transcription. While this is likely to be an important contributory factor, it has now become clear that the... 

Boffa, L.C., Walker, J., Chen, T.A., Sterner, R., Mariani, M.R., and Allfrey, V.G. (1990) Factors effecting nucleosome structure in transcriptionally active chromatin. Histone acetylation, nascent RNA and inhibitors of RNA synthesis. Eur. J. Biochem. 194, 811-823. 

Hebbes, T., Thorne, A.W., and Crane-Robinson, C. (1988) A direct link between core histone acetylation and transcriptionally active chromatin. EMBO J. 7, 1395-1403. 

Fig. 7. The model proposed by Szyf to explain the unmethylated status of active genes (for references and further details see Section 5.1). a) Inhibition of acetylation of the tails of core histones prevents active demethyiation. (b) When histone tails are acetylated, as in transcriptionally active chromatin regions, the demethyiase binding to the regions is enhanced, and the DNA is actively demethylated.

Evidence for a mechanism to exchange regulatory factors between the chromatin template and a nucleoplasmic compartment has been provided from imaging transcriptionally active chromatin loci in situ in live cells. Such studies have provided much information on the dynamics of histones and regulatory factors, as well as the large-scale organization of the loci in the context of the nuclear environment. 

Transcriptionally Active Chromatin Is Structurally Distinct from Inactive Chromatin... 

Many hypersensitive sites correspond to binding sites for known regulatory proteins, and the relative absence of nucleosomes in these regions may allow the binding of these proteins. Nucleosomes are entirely absent in some regions that are very active in transcription, such as the rRNA genes. Transcriptionally active chromatin tends to be deficient in histone HI, which binds to the linker DNA between nucleosome particles. 

Histones within transcriptionally active chromatin and heterochromatin also differ in their patterns of covalent modification. The core histones of nucleosome particles (H2A, H2B, H3, H4 see Fig. 24-27) are modified by irreversible methylation of Lys residues, phosphorylation of Ser or Thr residues, acetylation (see below), or attachment of ubiquitin (see Fig. 27-41). Each of the core histones has two distinct structural domains. A central domain is involved in histone-histone interaction and the wrapping of DNA around the nucleosome. A second, lysine-rich amino-terminal domain is generally positioned near the exterior of the assembled nucleosome particle the covalent modifications occur at specific residues concentrated in this amino-terminal domain. The patterns of modification have led some researchers to propose the existence of a histone code, in which modification patterns are recognized by enzymes that alter the structure of chromatin. Modifications associated with transcriptional activation would be recognized by enzymes that make the chromatin more accessible to the transcription machinery. 

Methylation of cytosine residues of CpG sequences is common in eukaryotic DNA (p. 296), but DNA in transcriptionally active chromatin tends to be undermethylated. Furthermore, CpG sites in particular genes are more often undermethylated in cells from tissues where the genes are expressed than in those where... 

Hypoacetylated, transcriptionally inactive chromatin assumes a more condensed structure and is more resistant to DNase I than hyperacetylated, transcriptionally active chromatin. 

DNA Strand Breaks and Poly(ADP-Ribosylated) Mediation of Transcriptionally Active Chromatin and Transforming Gene Stability... 

Reeves R (1984) Transcriptionally active chromatin. Biochim Biophys Acta 782 343-393... 

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