Histone variants and histone modifications in chromatin fractions from heterochromatin-rich Peromyscus cells

In order to investigate the relationship between condensed heterochromatin and histone modification by acetylation, phosphorylation and amino acid variation, chromatin from cultured Peromyscus eremicus cells, containing 35% constitutive heterochromatin, was fractionated into heterochromatin-enriched and heterochromatin-depleted fractions. The constitutive heterochromatin content of these fractions was determined from satellite DNA content. The distribution of phosphorylated and acetylated histones and amino acid variants of histone H2A in these chromatin fractions was examined by gel electrophoresis. Fractionation of histones demonstrated that endogenous histone phosphatase activity was high in chromatin fractions and could not be inhibited sufficiently to allow accurate histone phosphorylation measurements. However, sodium butyrate did inhibit deacetylation activity in the fractions, allowing histone acetylation measurements to be made. It was found that the constitutive heterochromatin content of these fractions was proportional to both their unacetylated H4 content and their more-hydrophobic H2A content. These observations support, by direct measurement, earlier experiments (Exp cell res 111 (1978) 373; 125 (1980) 377; 132 (1981) 201) suggesting that constitutive heterochromatin is enriched in unacetylated arginine-rich histones, and in the more hydrophobic variant of histone H2A.     

Histone modifications and nuclear architecture: a review.

Epigenetic modifications, such as acetylation, phosphorylation, methylation, ubiquitination, and ADP ribosylation, of the highly conserved core histones, H2A, H2B, H3, and H4, influence the genetic potential of DNA. The enormous regulatory potential of histone modification is illustrated in the vast array of epigenetic markers found throughout the genome. More than the other types of histone modification, acetylation and methylation of specific lysine residues on N-terminal histone tails are fundamental for the formation of chromatin domains, such as euchromatin, and facultative and constitutive heterochromatin. In addition, the modification of histones can cause a region of chromatin to undergo nuclear compartmentalization and, as such, specific epigenetic markers are non-randomly distributed within interphase nuclei. In this review, we summarize the principles behind epigenetic compartmentalization and the functional consequences of chromatin arrangement within interphase nuclei.     

Histone and histone fold sequences and structures: a database.

A database of aligned histone protein sequences has been constructed based on the results of homology searches of the major public sequence databases. In addition, sequences of proteins identified as containing the histone fold motif and structures of all known histone and histone fold proteins have been included in the current release. Database resources include information on conflicts between similar sequence entries in different source databases, multiple sequence alignments, and links to the Entrez integrated information retrieval system at the National Center for Biotechnology Information (NCBI). The database currently contains over 1000 protein sequences. All sequences and alignments in this database are available through the World Wide Web at: http: //www.ncbi.nlm.nih.gov/Baxevani/HISTONES/ .     

Special issue on epigenetic inheritance by histone modifications, histone variants and non-coding RNAs

Keeping in view the ever-growing importance of understanding the epigenetic phenomena shaping the behavior of life, our team decided to embark on the idea to organize this special issue of Frontiers in Biology on Epigenetics.Epigenetics refers to the study of heritable changes in gene expression without changes in DNA sequence, which is accomplished by DNA methylation, histone modifications, histone variants, chromatin remodeling, and non-coding RNAs.     

Histone dimers: a fundamental unit in histone assembly.

Histone interactions which occur, at moderate ionic strengths, when several types of purified, renatured histones are mixed at equimolar ratios have been studied. The four histones H2A,H2B,H3 and H4 complex and form dimers. Histone H1 does not interact with the other four histone types and does not form dimers. Mixing of single histone species with preformed histone pairs as well as mixing of two different types of histone pairs, leads to exchange of histones among the pairs and formation of dimers. No trimers are formed. The dimers are in equilibrium with high-molecular weight histone structures. The results indicate that histone dimers may serve as a stable intermediate in histone assembly. Because each histone type (except H1) can interact with itself as well as with each of the other three histone types we suggest that each histone type should be considered as an interchangeable subunit of a multichain protein in which the dimer species is the most stable structure.