Sequence elements in both subunits of the DNA fragmentation factor are essential for its nuclear transport.

DNA cleavage is a biochemical hallmark of apoptosis. In humans, apoptotic DNA cleavage is executed by DNA fragmentation factor (DFF) 40. In proliferating cells DFF40 is expressed in the presence of its chaperone and inhibitor DFF45, which results in the formation of the DFF complex.

Apoptotic DNA fragmentation is not related to the phosphorylation state of histone H1.

Changes in chromatin structure, histone phosphorylation and cleavage of DNA into nucleosome-size fragments are characteristic features of apoptosis. Since H1 histones bind to the site of DNA cleavage between nucleosomal cores, the question arises as to whether the state of H1 phosphorylation influences the rate of internucleosomal cleavage. Here, we tested the relation between DNA fragmentation and H1 phosphorylation both in cultured cells and in vitro.

Coordinate control and selective expression of the full complement of replication-dependent histone H4 genes in normal and cancer cells.

The replication of eukaryotic genomes necessitates the coordination of histone biosynthesis with DNA replication at the onset of S phase. The multiple histone H4 genes encode identical proteins, but their regulatory sequences differ. The contributions of these individual genes to histone H4 mRNA expression have not been described.

Subunits of the heterotrimeric transcription factor NF-Y are imported into the nucleus by distinct pathways involving importin beta and importin 13.

The transcriptional activator NF-Y is a heterotrimeric complex composed of NF-YA, NF-YB, and NF-YC, which specifically binds the CCAAT consensus present in about 30% of eukaryotic promoters. All three subunits contain evolutionarily conserved core regions, which comprise a histone fold motif (HFM) in the case of NF-YB and NF-YC. Our results of in vitro binding studies and nuclear import assays reveal two different transport mechanisms for NF-Y subunits.

Topoisomerase inhibitor induced dephosphorylation of H1 and H3 histones as a consequence of cell cycle arrest.

Posttranslational modifications of histones have an integral function in the structural and functional organization of chromatin. Several changes in the modification state of histones could be observed after induction of apoptosis with topoisomerase inhibitors and other inducers. Most of these studies include the analysis of the state of phosphorylation of histones, and the results are to some extent controversial, depending on cell lines and agents used.

Promoter modeling: the case study of mammalian histone promoters.

Motivation: Histone proteins play important roles in chromosomal functions. They are significantly evolutionarily conserved across species, which suggests similarity in their transcription regulation. The abundance of experimental data on histone promoters provides an excellent background for the evaluation of computational methods.

Human replication-dependent histone H3 genes are activated by a tandemly arranged pair of two CCAAT boxes.

We have analysed the transcriptional regulation of the human histone H3 genes using promoter deletion series, scanning mutagenesis, specific mutagenesis and electrophoretic mobility-shift assay experiments. The promoters of five of the six examined histone H3 genes showed near-maximal activity at lengths of 133-227 bp: H3/d 198 bp, H3/h 147 bp, H3/k 133 bp, H3/m 227 bp, H3/n 140 bp (exception H3/i). To search for functional cis-elements within these regions, we performed scanning mutagenesis of the two histone H3 promoters H3/k and H3/m.

Differential expression of human replacement and cell cycle dependent H3 histone genes.

Histones are the major protein component of chromatin. Except H4, all histone classes consist of several subtypes. The H3 family includes two replacement histone genes, H3.

Aberrant expression pattern of replication-dependent histone h3 subtype genes in human tumor cell lines.

We have determined the expression pattern of all 11 human replication-dependent histone H3 genes in three fetal human tissues (bladder, liver, and lung) and in eight human cell lines by RNase protection assay. In the fetal human tissues, all 11 genes were expressed to a varied extent. However, the relative contribution of each gene to the total replication-dependent histone H3 mRNA was rather similar in every tissue type.

Mytilus edulis core histone genes are organized in two clusters devoid of linker histone genes.

Comparison of histone gene cluster arrangements in several species has revealed a broad spectrum of histone gene patterns. To elucidate the core histone gene organization in a mollusk, we have analyzed a Mytilus edulis genomic library and have isolated eight phage clones containing core histone genes. Analysis of insert DNA revealed that the core histone genes are arranged as regular gene repeats of all four core histones.

The requirement of H1 histones for a heterodimeric nuclear import receptor.

After synthesis in the cytoplasm, H1 histones are imported into the nucleus through an energy-dependent process that can be mediated by an importin beta-importin 7 (Impbeta-Imp7) heterodimer. H1 histones contain two structurally different types of nuclear localization signals (NLS). The first type of NLS resides within the unstructured C-terminal domain and is rich in basic amino acids.