Heterochromatin structure

Foltz DR, Jansen LE, Black BE, Bailey AO, Yates JR, Cleveland DW (2006) The human CENP-A centromeric nucleosome-associated complex. Nat Cell Biol 8 458 69 Foresta C, Zorzi M, Rossato M, Varotto A (1992) Sperm nuclear instability and staining with aniline blue abnormal persistence of histones in spermatozoa in infertile men. Int J Androl 15 330-337 Fukagawa T, Nogami M, Yoshikawa M, Ikeno M, Okazaki T, Takami Y, Nakayama T, Oshimura M (2004) Dicer is essential for formation of the heterochromatin structure in vertebrate cells. Nat Cell Biol 6 784-791... 

Close observations of immunofluorescence signals showed that there are three different staining patterns, which correspond to three different nucleolar compartments FC (Fibrillar center), DFC (dense fibrillar component), and GC (granular component). Nucleolus is surrounded by heterochromatin. When the cells are in very active state of its proliferation, the nucleolar compartments and heterochromatin are integrated into a highly intricate structure called nucleolonema . A recent study has suggested that the chromatin associated with the nucleolus is less mobile than... 

Luger K, Mader, AW., Richmond RK, Sargent DF, Richmond TJ (1997) Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389 251-260 Ma Y, Jacobs SB, Jackson-Grusby L, Mastrangelo MA, Torres-Betancourt JA, Jaenisch R, Rasmussen TP (2005) DNA CpG hypomethylation induces heterochromatin reorganization involving the histone variant macroH2A. J Cell Sci 118 1607-1616... 

Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403 41-45 Suto RK, Clarkson MJ, Tremethick DJ, Luger K (2000) Crystal structure of a nucleosome core particle containing the variant histone H2A.Z. Nature Struct. Biol. 7 1121-1124 Swaminathan J, Baxter EM, Corces VG (2005) The role of histone H2Av variant replacement and histone H4 acetylation in the establishment of Drosophila heterochromatin. Genes Dev 19 65-76... 

Figure 1. Different histone chaperones in the key histone metabolic pathways Functions of histone chaperones range from the storage of newly synthesized histones in the cytoplasm, its transfer into the nucleus and in histone assembly into nucleosomes. Apart from diis die histone chaperones are also involved in histone exchange, maintenance of heterochromatin and in the regulation of chromatin structure during transcription. (See Colour Plate 10.)...

Herrera RE, Chen E, Weinberg RA (1996) Increased histone HI phosphorylation and relaxed chromatin structure in Rb-deficient fibroblasts. Proc Natl Acad Sci USA 93(21) 11510-11515 Hirota T, Lipp JJ, Toh BH, Peters JM (2005) Histone H3 serine 10 phosphorylation by Aurora B causes HPl dissociation from heterochromatin. Nature 438(7071) 1176—1180 Horn PJ, Carruthers LM, Logie C, Hill DA, Solomon MJ, Wade PA, Imbalzano AN, Hansen JC, Peterson CL (2002) Phosphorylation of linker histones regulates ATP-dependent chromatin remodeling enzymes. Nat Struct Biol 9(4) 263—267... 

Maison, C. et al. (2002) Higher-order structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA component. Nat. Genet. 30, 329-334. 

The structural differences between euchromatin and heterochromatin are coor-dinately regulated by reversible covalent modification of the DNA or histones. 

The effects of chromosome structure on gene regulation in eukaryotes have no clear parallel in prokaryotes. In the eukaryotic cell cycle, interphase chromosomes appear, at first viewing, to be dispersed and amorphous (see Figs 12-41, 24-25). Nevertheless, several forms of chromatin can be found along these chromosomes. About 10% of the chromatin in a typical eukaryotic cell is in a more condensed form than the rest of the chromatin. This form, heterochromatin, is transcriptionally inactive. Heterochromatin is generally associated... 

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. 

Chromatin structure is organized at several levels. The basic structure of chromatin—either heterochromatin or euchromatin—is called the nucleosome. The nucleosome is a complex of 146 base pairs of DNA, wound in two turns around the outside of a disk-like complex of eight proteins (called histones). The histone core contains two copies each of four histones, H2A, H2B, H3, and H4. The histone octamer is wrapped by very close to two turns of DNA. Linker DNA and another histone (HI) join together the nucleosomes (about 65 base pairs worth). HI binds cooperatively to nucleosomes, so that a gene can be zipped up all at once by the binding of many HI molecules successively. See Figure 12-1. 

A DNA modification which changes gene transcription is methylation of nucleotide bases. Heterochromatin contains heavily methylated DNA which cannot be transcribed. Genes in euchromatin are less methylated and are transcribable. Methylation at C5 of cytosine in CpG sequences by a methyltransferase, with 5-adenosyl methionine (SAM) as methyl donor, silences genes in heterochromatin. Methylation may affect the higher-order structure of DNA and may impede access of the transcriptional machinery to DNA. Members of the histone Hj family have been associated with transcriptional repression, because these histones bind preferentially to methylated CpG sequences (Fig. 9.10).4i... 

---