Transcription, histone association with

Spencer, V.A. and Davie, J.R. (2001) Dynamically acetylated histone associated with transcriptionally active and competent genes in the avian adult beta-globin gene domain. J. Biol. Chem. 276, 34810-34815. 

Repression of genes is associated with reversal of this process under the control of histone deacetylases (HDACs). Deacetylation of histones increases the winding of DNA round histone residues, resulting in a dense chromatin structure and reduced access of transcription factors to their binding sites, thereby leading to repressed transcription of inflammatory genes. 

Acetylation of histones H3 and H4 is associated with the activation or inactivation of gene transcription (Chapter 37). 

H2A Barr body-deficient (Bbd) is an evolutionary relatively young histone variant sharing only about 48% amino acid sequence similarity to H2A. This histone variant appears to be specific for mammals (Chadwick and Willard 2001). As indicated by the name, the transcriptionally inactive and highly condensed X chromosome in female mammals (also known as Barr body ) is depleted for H2A , while this variant is detectable in autosomes and the active sex chromosomes. This observation suggested that H2A is linked to transcriptionally active euchromatin. H2A cofractionates in sedimentation centrifugation with hyper-acetylated histone H4, further corroborating that it associates with transcriptionally active euchromatin. 

Depletion of histone HI after covalent modification from chromatin is a key step in eukaryotic transcription (Lee et al, 1993 Juan et al, 1994 Rice and Allis, 2001). A comparison of the association of the antibiotic Mg + complexes with the normal and HI depleted chromatin suggests that smaller ligands, like anticancer drugs, have better accessibility for HI depleted chromatin compared to native chromatin. HI depleted chromatin is also more prone to aggregation upon association with the complex I of the antibiotic Mg + complexes. It is also less accessible to micrococcal nuclease. We propose that HI depleted chromatin is a better target of these antibiotics compared to native chromatin. This observation is particularly significant in case of neoplastic cells where most of the cell nuclei are transcriptionally active, and, therefore, contain HI depleted chromatin. 

Shigeno K, Yoshida H, Pan L, Luo JM, Fujisawa S, Naito K, Nakamura S, Shinjo K, Takeshita A, Ohno R, Ohnishi K (2004) Disease-related potential of mutations in transcriptional cofactors CREB-binding protein and p300 in leukemias. Cancer Lett. 213 11—20 Shiio Y, Eisenman RN (2003) Histone sumoylation is associated with transcriptional repression. Proc Natl Acad Sci U S A 100 13225-13230... 

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