A highly conserved sequence in H1 histone genes as an oligonucleotide hybridization probe: Isolation and sequence of a duck H1 gene

A 3.5-kb HindIII fragment of a histone gene cluster was isolated from a recombinant phage out of a duck genomic library. This DNA contains a duck H1 gene and its flanking sequences. The hybridization probe, which was used to screen for the H1 gene, had been designed on the basis of a comparative analysis of available H1 gene and protein data. Most H1 histones contain repeated motifs in their C-terminal domain, and these form part of an octapeptide (ser pro lys lys ala lys lys pro) that is highly conserved in many H1 histone proteins. A comparison of the duck H1 described here with two different published chicken H1 histone sequences reveals conservative amino acid exchanges at 22 (of 217 and 218, respectively) positions. The homology is maintained at the flanking sequences, and includes the putative H1 histone gene-specific signal structures and the established 3' stem and loop structures and the CAAGA box. The duck H1 gene and its flanking sequence have been found in identical arrangements in two recombinant bacteriophages, but minor sequence variations and genomic Southern blotting after HindIII digestion suggest that we have either isolated alleles of this genome segment or that the gene described may occur twice per haploid duck genome.     

Preserving genome integrity and function: the DNA damage response and histone modifications

Modulation of chromatin templates in response to cellular cues, including DNA damage, relies heavily on the post-translation modification of histones. Numerous types of histone modifications including phosphorylation, methylation, acetylation, and ubiquitylation occur on specific histone residues in response to DNA damage. These histone marks regulate both the structure and function of chromatin, allowing for the transition between chromatin states that function in undamaged condition to those that occur in the presence of DNA damage. Histone modifications play well-recognized roles in sensing, processing, and repairing damaged DNA to ensure the integrity of genetic information and cellular homeostasis. This review highlights our current understanding of histone modifications as they relate to DNA damage responses (DDRs) and their involvement in genome maintenance, including the potential targeting of histone modification regulators in cancer, a disease that exhibits both epigenetic dysregulation and intrinsic DNA damage.     

Evidence for dynamic alteration in histone gene clusters of Caenorhabditis elegans: a topoisomerase II connection?

Chromatin integrity is maintained throughout the cell cycle through repair mechanisms and intrinsically by the ordered packaging of DNA in association with histone proteins; however, aberrant rearrangements within and between chromosomes do occur. The role of the nuclear matrix protein topoisomerase II (TopoII) in generating chromosome breakpoints has been a focus of recent investigations. TopoII preferentially binds in vitro to scaffold-associated regions (SARs) and is involved in many DNA processing activities that require chromosome untangling. SARs, biochemically defined DNA elements rich in A + T, have been proposed to serve as structural boundaries for chromatin loops and to delineate functional domains. In our investigation of gene compartmentalization in a eukaryotic genome, SAR-associated nucleotide motifs from Drosophila were mapped in the regions of three histone gene clusters in an in silico analysis of the genome of Caenorhabditis elegans. Sites with similarity to the 15 bp consensus for TopoII cleavage were found predominantly in A + T enriched intergenic regions. Reiteration of sites matching the TopoII core consensus led to the identification of a novel core histone gene on chromosome IV and provided evidence for duplication and inversion in each of the three histone gene clusters. Breakpoint analysis of DNA flanking reiterated regions revealed potential sites for TopoII cleavage and a base composition phenomenon suggestive of a trigger for inversion events.     

CTCF, cohesin, and histone variants: connecting the genome

During the last decades our view of the genome organization has changed. We moved from a linear view to a looped view of the genome. It is now well established that inter- and intra-connections occur between chromosomes and play a major role in gene regulations. These interconnections are mainly orchestrated by the CTCF protein, which is also known as the "master weaver" of the genome. Recent advances in sequencing and genome-wide studies revealed that CTCF binds to DNA at thousands of sites within the human genome, providing the possibility to form thousands of genomic connection hubs. Strikingly, two histone variants, namely H2A.Z and H3.3, strongly co-localize at CTCF binding sites. In this article, we will review the recent advances in CTCF biology and discuss the role of histone variants H2A.Z and H3.3 at CTCF binding sites.     

Broad Chromatin Domains: An Important Facet of Genome Regulation

Chromatin composition differs across the genome, with distinct compositions characterizing regions associated with different properties and functions. Whereas many histone modifications show local enrichment over genes or regulatory elements, marking can also span large genomic intervals defining broad chromatin domains. Here we highlight structural and functional features of chromatin domains marked by histone modifications, with a particular emphasis on the potential roles of H3K27 methylation domains in the organization and regulation of genome activity in metazoans.     

Histone H1 Genes and Histone Gene Clusters in the Genus Drosophila

Whereas the genomes of many organisms contain several nonallelic types of linker histone genes, one single histone H1 type is known in Drosophila melanogaster that occurs in about 100 copies per genome. Amplification of H1 gene sequences from genomic DNA of wild type strains of D. melanogaster from Oregon, Australia, and central Africa yielded numerous clones that all exhibited restriction patterns identical to each other and to those of the known H1 gene sequence. Nucleotide sequences encoding the evolutionarily variable domains of H1 were determined in two gene copies of strain Niamey from central Africa and were found to be identical to the known H1 sequence. Most likely therefore, the translated sequences of D. melanogaster H1 genes do not exhibit intragenomic or intergenomic variations. In contrast, three different histone H1 genes were isolated from D. virilis and found to encode proteins that differ remarkably from each other and from the H1 of D. melanogaster and D. hydei. About 40 copies of H1 genes are organized in the D. virilis genome with copies of core histone genes in gene quintets that were found to be located in band 25F of chromosome 2. Another type of histone gene cluster is present in about 15 copies per genome and contains a variable intergenic sequence instead of an H1 gene. The H1 heterogeneity in D. virilis may have arisen from higher recombination rates than occur near the H1 locus in D. melanogaster and might provide a basis for formation of different chromatin subtypes. Received: 2 March 2000 / Accepted: 1 June 2000     

Mass spectrometry analysis of the variants of histone H3 and H4 of soybean and their post-translational modifications

Background  

Histone modifications and histone variants are of importance in many biological processes. To understand the biological functions of the global dynamics of histone modifications and histone variants in higher plants, we elucidated the variants and post-translational modifications of histones in soybean, a legume plant with a much bigger genome than that of Arabidopsis thaliana.     

Differential in vivo binding dynamics of somatic and oocyte-specific linker histones in oocytes and during ES cell nuclear transfer

The embryonic genome is formed by fusion of a maternal and a paternal genome. To accommodate the resulting diploid genome in the fertilized oocyte dramatic global genome reorganizations must occur. The higher order structure of chromatin in vivo is critically dependent on architectural chromatin proteins, with the family of linker histone proteins among the most critical structural determinants. Although somatic cells contain numerous linker histone variants, only one, H1FOO, is present in mouse oocytes. Upon fertilization H1FOO rapidly populates the introduced paternal genome and replaces sperm-specific histone-like proteins. The same dynamic replacement occurs upon introduction of a nucleus during somatic cell nuclear transfer. To understand the molecular basis of this dynamic histone replacement process, we compared the localization and binding dynamics of somatic H1 and oocyte-specific H1FOO and identified the molecular determinants of binding to either oocyte or somatic chromatin in living cells. We find that although both histones associate readily with chromatin in nuclei of somatic cells, only H1FOO is capable of correct chromatin association in the germinal vesicle stage oocyte nuclei. This specificity is generated by the N-terminal and globular domains of H1FOO. Measurement of in vivo binding properties of the H1 variants suggest that H1FOO binds chromatin more tightly than somatic linker histones. We provide evidence that both the binding properties of linker histones as well as additional, active processes contribute to the replacement of somatic histones with H1FOO during nuclear transfer. These results provide the first mechanistic insights into the crucial step of linker histone replacement as it occurs during fertilization and somatic cell nuclear transfer.     

Histone gene transposition in the phylogeny of the Drosophila obscura group

The chromosomal location of the histone genes was determined in seven species of the Drosophila obscura group by in situ hybridization. Histone genes occur on more than one site per genome and on non-homologous chromosome elements. In addition, the metaphase karyotypes and the banding pattern of the polytene chromosomes were compared. Based on chromosomal characters, the cladogenesis of the D. obscura group was established. From the distribution of histone sites in different species, analysed in this paper and in previous studies, the phylogenetic history of histone gene transposition was derived. The molecular mechanisms responsible for the generation of new histone sites are discussed.     

Histone tails: Directing the chromatin response to DNA damage

Considerable energetic investment is devoted to altering large stretches of chromatin adjacent to DNA double strand breaks (DSBs). Immediately ensuing DSB formation, a myriad of histone modifications are elicited to create a platform for inducible and modular assembly of DNA repair protein complexes in the vicinity of the DNA lesion. This complex signaling network is critical to repair DNA damage and communicate with cellular processes that occur in cis and in trans to the genomic lesion. Failure to properly execute DNA damage inducible chromatin changes is associated with developmental abnormalities, immunodeficiency, and malignancy in humans and in genetically engineered mouse models. This review will discuss current knowledge of DNA damage responsive histone changes that occur in mammalian cells, highlighting their involvement in the maintenance of genome integrity.     

Computer- and structure-based lead design for epigenetic targets

The term epigenetics is defined as inheritable changes that influence the outcome of a phenotype without changes in the genome. Epigenetics is based upon DNA methylation and posttranslational histone modifications. While there is much known about reversible acetylation as a posttranslational modification, research on reversible histone methylation is still emerging, especially with regard to drug discovery. As aberrant epigenetic modifications have been linked to many diseases, inhibitors of histone modifying enzymes are very much in demand. This article will summarize the progress on small molecule epigenetic inhibitors identified by structure- and computer-based approaches.     

Histone transfer among chaperones

The eukaryotic processes of nucleosome assembly and disassembly govern chromatin dynamics, in which histones exchange in a highly regulated manner to promote genome accessibility for all DNA-dependent processes. This regulation is partly carried out by histone chaperones, which serve multifaceted roles in co-ordinating the interactions of histone proteins with modification enzymes, nucleosome remodellers, other histone chaperones and nucleosomal DNA. The molecular details of the processes by which histone chaperones promote delivery of histones among their many functional partners are still largely undefined, but promise to offer insights into epigenome maintenance. In the present paper, we review recent findings on the histone chaperone interactions that guide the assembly of histones H3 and H4 into chromatin. This evidence supports the concepts of histone post-translational modifications and specific histone chaperone interactions as guiding principles for histone H3/H4 transactions during chromatin assembly.     

Genome-wide patterns of histone modifications in yeast

Post-translational histone modifications and histone variants generate complexity in chromatin to enable the many functions of the chromosome. Recent studies have mapped histone modifications across the Saccharomyces cerevisiae genome. These experiments describe how combinations of modified and unmodified states relate to each other and particularly to chromosomal landmarks that include heterochromatin, subtelomeric chromatin, centromeres, origins of replication, promoters and coding regions. Such patterns might be important for the regulation of heterochromatin-mediated silencing, chromosome segregation, DNA replication and gene expression.     

多倍体植物的表观遗传现象

表观遗传现象是指基因表达发生改变但不涉及DNA序列的变化, 它存在于许多植物的多倍体化过程中,而且能够在代与代之间传递。表观遗传变异包括基因沉默、DNA甲基化、核仁显性、休眠转座子激活和基因组印记等方面。这种现象可能是由于基因组间的相互作用直接诱发基因沉默或基因表达改变所致;也可能由DNA甲基化之外的组蛋白编码的改变引起;或者与甲基化不足、染色质重组或转座子激活等有关。表观遗传变异在提高基因表达的多样性,引起遗传学和细胞学上的二倍化,以及促进基因组间的相互协调等方面起着重要作用。文章综述了植物多倍体化过程中的表观遗传现象及其在多倍体植物基因组进化中的作用,并在此基础上提出了今后在这方面的研究途径。