Organization of human histone genes.

Abstract

We describe the isolation and initial characterization of seven independent A Charon 4A recombinant phages which contain human histone genomic sequences (designated AHHG). Restriction maps of these clones and localization of the genes coding for histones H2A, H2B, H3, and H4 are presented. The presence of histone encoding regions in the AHHG clones was demonstrated by several independent criteria including hybridization with specific DNA probes, hybrid selection/in vitro translation, and hybridization of AHHG DNAs to reverse Southern blots containing cytoplasmic RNAs from G1-, S-, and arabinofuranosylcytosine (cytosine arabinoside)-treated S-phase cells. In addition, the AHHG DNAs were shown to protect in vivo labeled H4 mRNAs from S1 nuclease digestion. Based on the analysis of the AHHG clones, human histone genes appear to be clustered in the genome. However, gene clusters do not seem to be present in identical tandem repeats. The AHHG clones described in this report fall into at least three distinct types of arrangement. One of these arrangements contains two coding regions for each of the histones H3 and H4. This RNA is not similar in size to known histone-encoding RNAs and is present in the cytoplasm ofHeLa cells predominantly in the G1 phase of the cell cycle.Histone proteins complex with DNA to form structures, known as nucleosomes, that are fundamental components in the organization of the eukaryotic genome. The synthesis of histone proteins is tightly coupled to DNA replication in a number of higher eukaryotic cells (1-4). Although more definitive experiments are required, several lines ofevidence point toward transcriptional level control of histone gene expression during the cell cycle in HeLa cells and in normal human diploid fibroblasts (5-10). To elucidate the levels and mechanisms of human histone gene regulation, homologous probes specific for individual histone genes, as well as knowledge about the structure and organization of the human histone genes, are required. Cloned human genomic histone sequences should provide such specific probes and are requisite for the identification of those DNA sequences involved in the regulation of these genes. Histone genes of several other species have been cloned and characterized. In sea urchins and Drosophila melanogaster these genes are clustered and tandemly repeated (reviewed in ref. 11), whereas in yeast (12), mouse (13,14), and chicken (15, 16) the histone genes are also clustered but have no apparent repeat.In this paper, we report the isolation and initial character- (19). Phage DNA was isolated by a modification of the method described by Blattner (18). All experiments involving viable bacteriophage and bacteria containing recombinant DNA were performed under conditions specified by the National Institutes of Health guidelines for research involving recombinant DNA.Gene-Specific Histone Probes. Cloned genomic chicken sequences containing H3 and H4 encoding regions were used to screen the human recombinant library. Gene localization in the ...

Histone gene number and organisation inXenopus: Xenopus borealishas a homogeneous major cluster

“…The picture that is emerging of histone gene organization in animals is that all contain a set of variant clusters in low copy number (6,11,12,13,14), and all except mammals and birds also contain a reiterated, homogeneous family of clusters. In the case of sea urchins it is known that the highly reiterated genes are expressed in early development (2,3), when the high copy number is demanded by the requirement for rapid mRNA synthesis (36,37).…”

“…In mammals and birds there are only 10-20 histone genes (8,9,10) and although they are clustered, there is no major type of cluster appparent (11,12,13,14). Furthermore, cloned clusters from chicken, mouse and man often contain more than one copy of a particular histone type (11,12,13,14).…”

“…Furthermore, cloned clusters from chicken, mouse and man often contain more than one copy of a particular histone type (11,12,13,14).…”

H1 histone synthesis by implanting pig blastocysts

“…The histone variants, especially the HI variants, may in turn be related to changes in chromatin structure and changes in overall transcription activity which occur as development proceeds (Arceci & Gross, 1981). There are indications that the shift in HI histone type, from the earlier to the later variant, is not a result of the process of differentiation (Brookbank, 1978(Brookbank, , 1980(Brookbank, , 1982Arceci & Gross, 1980) (Kunkel & Weinberg, 1978;Kedes & Maxson, 1981 (Kedes & Maxson, 1981 ;Sierra et al, 1982).…”

Effect of adenovirus infection on expression of human histone genes.

“…Structural analysis of human histone genes has indicated that they are anatomically and functionally uncomplicated, lacking intervening sequences and polyadenylate tracts (10,20,40,41). Moreover, histone mRNA species can be found in functional form in polyribosomes within minutes of transcription of histone genes (reviewed in reference 46).…”