Biomedical subjects

D Doenecke

Publications and source records attributed to D Doenecke.

At least 55 records · Page 3Linked to original sources

PubMed1996

Testis-specific expression of a novel human H3 histone gene.

We have investigated the expression of a recently described, solitary human H3 histone gene. Using RNase protection assays, the corresponding mRNA could only be detected in RNA preparations from human testis, whereas several human cell lines and somatic tissues did not exhibit expression of this gene. In situ hybridization of sections from human testis revealed expression to be confined to primary spermatocytes. In addition to H1t, this novel H3 gene, which is located on chromosome 1, is the second tissue-specific human histone gene that has been found to be expressed solely in the testis.

Adult↗

PubMed1996

A solitary human H3 histone gene on chromosome 1.

A solitary histone H3 gene encoding a novel H3 protein sequence has been isolated. This H3 gene maps to chromosome 1 (1q42), whereas we have shown previously that the majority of the human histone genes form a large cluster on chromosome 6 (6p21.3). In addition, a small cluster has been described at 1q21. The clustered histone genes are expressed during the S-phase of the cell cycle, hence their definition as replication-dependent histone genes. In contrast, expression of replacement histone genes is essentially cell-cycle independent; they are solitary genes and map outside the major clusters. The newly described H3 gene maps outside all known histone gene clusters and varies by four amino acid residues from the consensus mammalian H3 structure. In contrast to other solitary histone genes, this human H3 gene shows the consensus promoter and 3' flanking portions that are typical for replication-dependent genes.

Base Sequence↗

PubMed1996

Expression of the mouse testicular histone gene H1t during spermatogenesis.

The testicular H1 histone variant, H1t, is synthesized during spermatogenesis in mammalian male germ cells. In situ hybridization and immunohistochemical techniques were used to assign the expression of either the H1t mRNA or the H1t protein to specific cell stages of spermatogenesis. Our results show the presence of the H1t mRNA only in the late and mid-pachytene stages, whereas the protein occurs first in pachytene spermatocytes, and persists until later stages from round up to elongated spermatids.

Animals↗

PubMed1996

Chromosome mapping of rat histone genes H1fv, H1d, H1t, Th2a and Th2b.

Chromosome assignment of the rat histone genes H1t, H1d (H1.4), H1fv (H10), Th2a and Th2b is described. The testicularly expressed histone genes H1t, Th2a and Th2b could be assigned to rat chromosome (RNO) 17 by PCR analysis of somatic cell hybrid DNAs. The H1d gene was mapped to RNO17p12-->p11 by FISH. These genes might form a histone gene cluster homologous to that found on HSA6p21.3 in humans and MMU13A2-3 in mice. The rat histone H1fv gene was assigned to RNO7 by PCR. This result allows the inclusion of rat H1fv to an established conserved group of syntenic genes in rat, mouse and human on chromosomes RNO7, MMU15 and HSA22, respectively.

Animals↗

PubMed1996

Organization and expression of the developmentally regulated H1(o) histone gene in vertebrates.

The H1 class of histones comprises several main-type, S-phase dependent isoforms and, in addition, a sperm-specific H1t and a peculiar subtype, H1 zero, which is confined to highly differentiated cells. In contrast to main type histone genes, the H1 zero gene expression does not strictly depend on DNA replication. Also in contrast to the other H1 subtype genes, the mammalian H1 zero gene is not included in a histone gene cluster and its mRNA differs in structure, size and mode of processing from other histone mRNAs. The regulation of expression of the H1 zero gene varies from main type H1 genes in several respects. This is manifested in the promoter structure which contains sequence elements that are also found in main type H1 promoters, but also shows regulatory motifs which appear to be involved in a developmental regulation of the H1 zero gene, such as a retinoic acid receptor binding site, which has been described in the mammalian H1 zero gene promoter.

Animals↗

PubMed1995

The human replacement histone H3.3B gene (H3F3B).

H3.3 is a replacement histone subtype that is encoded by two replication-independent genes termed H3.3A and H3.3B, respectively. We have isolated a fullsize H3.3 cDNA clone from an oligo(dT)-primed human testicular cDNA library. Subsequently, the corresponding gene was isolated from a human cosmid library and was identified as the H3.3B gene. It was the only histone gene on this 42-kb cosmid clone. The gene structure shows characteristic features of an H3.3 gene. First, it contains an intron of about 0.5 kb in the 5' untranslated region and two smaller introns within the coding gene portion. Second, no histone gene-specific dyad symmetry element was found in the 3' untranslated region, but three putative polyadenylation signals were detected downstream of the gene. The corresponding transcripts were detected by Northern blot analysis using poly(A)+ RNA from testis and from the HEK293 tumor cell line. The newly discovered human H3.3B gene (HGMW-approved symbol H3F3B) was mapped by fluorescence in situ hybridization to the telomeric region of chromosome 17 (17q25). This localization of the H3.3B gene and its solitary arrangement contrast with the majority of the replication-dependent histone genes, which form a large cluster on chromosome 6 and a second cluster on chromosome 1.

Amino Acid Sequence↗

PubMed1995

Isolation of two murine H1 histone genes and chromosomal mapping of the H1 gene complement.

The mammalian H1 histone gene complement consists of at least seven H1 protein isoforms. These include five S-phase-dependent H1 protein subtypes and two more distantly related proteins, which are expressed upon terminal differentiation (H1o) or during the pachytene stage of spermatogenesis (H1t). In the past, three replication-dependent murine H1 genes plus the H1o and H1t genes have been isolated and characterized. In this report, we describe the sequences of two more H1 genes, and we show that all five murine replication-dependent H1 genes and the H1t gene map to the region A2-3 on Chromosome (Chr) 13. This is in agreement with our previous finding that the human H1 histone gene complement maps to 6p21.3, which corresponds to the A2-3 region on the murine Chr 13. Previous reports have shown that the replication-independent H1o genes map to syntenic regions on Chrs 22 (human H1o) and 15 (murine H1o).

Amino Acid Sequence↗

PubMed1995

Association of histone H4 genes with the mammalian testis-specific H1t histone gene.

Mouse and human H4 genes associated with the testis-specific H1t gene were isolated from genomic libraries and were sequenced. The deduced amino acid sequences are identical to other mouse or human H4 histones, but the genes differ significantly in their nucleotide sequences. Both the human and the mouse genes are located on the same DNA strand compared with the H1t gene. In contrast to this identical transcriptional orientation of H1t and its neighboring H4 gene in mouse and man, an H4 gene with the opposite orientation has been described in the vicinity of the rat H1t gene. Northern blot analysis of RNA from testicular cells separated by centrifugal elutriation, S1 nuclease mapping, and reverse transcriptase polymerase chain reaction (RT-PCR) amplification show that both the murine and human H4 genes, like the H1t gene, are expressed in testicular cells, whereas the H4 genes, in contrast to the H1t gene, are expressed in nontesticular human and mouse cell culture cells.

Amino Acid Sequence↗

PubMed1995

Regulation of H1(0) gene expression by nuclear receptors through an unusual response element: implications for regulation of cell proliferation.

Cloning and sequence analysis of the 5'-flanking region of the human H1(0) histone gene, a differentiation-specific member of the H1 family, has revealed several potential regulatory elements. In this study, we have characterized the interactions of nuclear receptors with an unusual response element consisting of two half-sites arranged as a direct repeat with an 8-bp spacer (DR-8). Thyroid hormone receptors (TR) bind this DR-8 as homodimers and heterodimers with RXR. Retinoic acid receptors (RARs) also bind as heterodimers with RXR to the DR-8, and this binding is enhanced in the presence of retinoic acid (RA) and/or 9-cis RA. Reporter constructs containing the DR-8 allowed a several-fold induction by T3 in the presence of TRs. RAR alpha and RAR beta allowed RA-dependent transcriptional activation whereas RAR gamma mostly increased basal activity. 9-cis RA inhibited the T3 response, indicating a hormonal cross-talk among the subfamily of nuclear receptors. Two orphan receptors, COUP-TF and v-erbA, also bind the DR-8 sequence in the human H1(0) promoter. COUP-TF, which usually represses RAREs, enhances transcriptional activation through the DR-8 whereas v-erbA completely represses TR-RXR induction of the H1(0) gene. Thus, a number of signaling pathways that play important roles during development and differentiation are able to influence the transcription rate of this special H1 subtype directly through a DR-8 response element in its promoter. Because H1(0) expression levels inversely correlate with cell proliferation, our data suggest that several nuclear receptors and the v-erbA oncogene can influence cell proliferation via the regulation of H1(0) expression.

Base Sequence↗

PubMed1995

Structure of histone H2B and H4 genes of the sea cucumber Holothuria tubulosa.

A genomic library of the sea cucumber Holothuria tubulosa was screened with human and murine histone gene hybridization probes. A recombinant phage carrying an H4 gene was isolated and sequenced. Hybridization analysis of the entire 20 kb phage insert with probes for H1, H2A, H2B and H3 histones was negative except for H2B. This solitary arrangement of the two neighbouring histone H4 and H2B genes is in contrast to the organization of 'cleavage stage' histone genes, which are arranged in tandem quintets of genes encoding the 5 histone classes. Gene organization and sequence features indicate that the two Holothuria genes are the equivalents of a known pair of late H2B and H4 genes which have been described in the genome of sea urchins. This result shows that the simultaneous occurrence of tandem repeats of histone gene quintets and smaller groups of structurally distinct histone gene subtypes is not unique for sea urchins, but also applies to other echinodermata, such as the sea cucumber Holothuria tubulosa.

Amino Acid Sequence↗

PubMed1994

Role of a distal promoter element in the S-phase control of the human H1.2 histone gene transcription.

The expression of one of the human main type H1 histone genes (termed H1.2) appears to be regulated by several trans-acting factors. Upstream of consensus regulatory regions, such as the TATA-, CCAAT- and H1-box (AAACACA) sequences, a crucial control site is located between nucleotide positions -536 and -412 (relative to the ATG initiation site). Removal of this promoter portion causes in chloramphenicol acetyl transferase reporter gene constructs a loss of the S-phase control function of the H1.2 promoter in HeLa cells. Electrophoretic mobility-shift assay and DNase I footprinting analysis suggest that the H1-box variant AAACAGA is a potential control element within the distal promoter region.

Aphidicolin↗

PubMed1994

Organization and expression of H1 histone and H1 replacement histone genes.

The H1 family is the most divergent subgroup of the highly conserved class of histone proteins [Cole: Int J Pept Protein Res 30:433-449, 1987]. In several vertebrate species, the H1 complement comprises five or more subtypes, and tissue specific patterns of H1 histones have been described. The diversity of the H1 histone family raises questions about the functions of different H1 subtypes and about the differential control of expression of their genes. The expression of main type H1 genes is coordinated with DNA replication, whereas the regulation of synthesis of replacement H1 subtypes, such as H1 zero and H5, and the testis specific H1t appears to be more complex. The differential control of H1 gene expression is reflected in the chromosomal organization of the genes and in different promoter structures. This review concentrates on a comparison of the chromosomal organization of main type and replacement H1 histone genes and on the differential regulation of their expression. General structural and functional data, which apply to both H1 and core histone genes and which are covered by recent reviews, will not be discussed in detail.

Amino Acid Sequence↗

PubMed1994

Expression and chromosomal mapping of the gene encoding the human histone H1.1.

The expression of a human histone H1 isoform (H1.1) was studied in several human tissues. Northern blot analysis has revealed that this gene is expressed in testis and thymus, but not in other human tissues. In this report, we demonstrate that the expression of the histone H1.1 gene in human testis is restricted to early round spermatids that belong to the fraction of postmeiotic sperm cells. Transcripts hybridizing with the human H1.1 gene could not be detected in testis of mouse, rat, bull or boar. Southern blot analysis with human genomic DNA, DNA from different Old World monkeys (chimpanzee, orangutan, gorilla and rhesus monkey) and DNA from several mammalian species has revealed that the histone H1.1 gene is highly conserved in higher primates, whereas no cross-hybridization can be detected with DNA from other mammalian species such as mouse, rat, hamster or bull. In a previous report, the human histone H1.1 gene and other H1 genes (H1.2-H1.5, H1t) were assigned to chromosome 6 by polymerase chain reaction analysis using human-rodent cell hybrid DNA; fluorescence in situ hybridization indicated that these genes form part of a major gene cluster on the short arm of chromosome 6. We have confirmed the localization of histone H1.1 to chromosome 6 and have regionally assigned the locus to 6p21.3 by radioactive in situ hybridization.

Blotting, Southern↗

PubMed1994

Histone H1 zero: a major player in cell differentiation?

Histone H1 zero was initially described as a member of the lysine-rich histone class, typically present in nondividing mammalian cells. Since then it has been found in almost every animal or plant species studied. The protein accumulates in terminally differentiated cells that have stopped dividing. It has also been implicated in changes in chromatin structure and function accompanying malignant transformation. Despite its involvement in these fundamental cellular processes, its precise role remains elusive, as do the molecular mechanisms via which it acts. This review is an attempt to summarize and critically discuss the huge relevant literature, trying to highlight the problems that still await answers.

Animals↗

PubMed1993

Structure and expression of the mouse testicular H1 histone gene (H1t).

A mouse genomic library was screened with a human testicular H1 (H1t) gene fragment. One phage containing the testis specific mouse H1t histone gene and its flanking regions was isolated. Northern blot analysis showed that the mouse H1t gene is expressed only in mouse testis at the stage of pachytene spermatocytes and that the H1t mRNA is not polyadenylated. This mouse H1t gene encodes a protein which differs from the somatic mouse H1 proteins, but is similar to the known H1t proteins from rat, and man.

Amino Acid Sequence↗

PubMed1993

A rat histone H2B pseudogene is closely associated with the histone H1d gene.

A 9 kb EcoRI restriction fragment was isolated from a recombinant phage out of a rat genomic library. This DNA fragment contains a rat H1d histone gene, its flanking sequences and a H2B histone pseudogene closely associated with the H1d gene. A comparison of the H2B pseudogene with human H2B genes flanking regions reveals sequence homologies to a human H2B histone gene (Albig, W. et al. (1991) Genomics 10, 940-948).

Amino Acid Sequence↗

PubMed1993

Association of a human H1 histone gene with an H2A pseudogene and genes encoding H2B.1 and H3.1 histones.

A cluster of human histone genes was found on three overlapping clones isolated from cosmid and bacteriophage libraries. These three overlapping segments of the human genome comprise genes coding for H3.1, an H2A pseudogene, and an H2B.1 gene downstream of the previously characterized H1.2 gene. The cosmid clone covers 30 kb upstream of the H1.2 gene and overlaps with two phage clones covering the core histone genes and the pseudogene. The same arrangement of an H3 gene, an H2A pseudogene and an H2B gene downstream of an H1 gene has been described within a mouse histone gene cluster [Yang et al.:J Biol Chem 262:17118-17125, 1987; Gruber et al.:Gene 95:303-304, 1990].

Amino Acid Sequence↗

PubMed1993

All known human H1 histone genes except the H1(0) gene are clustered on chromosome 6.

PCR analysis of chromosomal DNA from a panel of human-rodent somatic cell hybrids revealed that the five human H1 histone genes H1.1 to H1.5 and the gene encoding the testis-specific H1t subtype, all of which form clusters with core histone genes, are located on chromosome 6. The H1(0) subtype, which is not neighbored by core histone genes, maps to chromosome 22. Fluorescence in situ hybridization with human metaphase chromosomes and PCR analysis of somatic cell hybrid DNA carrying only fragments of chromosome 6 revealed the region 6p21.1 to 6p22.2 as the histone gene cluster region.

Animals↗