Nuclear basic proteins in spermiogenesis

Wouters-Tyrou, Danièle; Martinage, Arlette; Chevaillier, Philippe; Sáutière, Pierre

doi:10.1016/s0300-9084(98)80018-7

Cited by 152 publications

(113 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…During spermiogenesis, the sperm nucleus undergoes genome-wide reorganization, which involves the removal of histones and their replacement by various nuclear proteins, including highly positively charged protamines [Wouters-Tyrou et al 1998;Sassone-Corsi 2002]. Humans express two types of protamines, protamine 1 (P1) and protamine 2 (P2), expressed in the post-meiotic haploid spermatid and stored in messenger ribonuclear protein (mRNP) particles [Steger et al 1998;Steger 1999], and translated in the elongating spermatid [Steger 2001;Steger et al 2002].…”

Section: Introductionmentioning

confidence: 99%

Identification of Genetic Variation in the 5′ and 3′ Non-coding Regions of the Protamine Genes in Patients with Protamine Deregulation

Hammoud

Emery

Aoki

et al. 2007

Archives of Andrology

View full text Add to dashboard Cite

Deregulation of sperm nuclear protamine ratio (P1=P2) has been shown to correlate with male factor infertility in humans, but the cause of this abnormal protein expression has yet to be identified. Recent studies have shown that there is little genetic variability in the coding regions of either of the protamine gene sequences. However, these studies did not investigate the 5 0 or 3 0 non-coding regions of these genes for mutations that might account for changes in the transcriptional or translational regulation of the protamines.In an effort to determine if genetic variation in these non-coding regions may account for aberrant protamine expression, we have sequenced the 5 0 and 3 0 untranslated regions (UTRs) of both protamine 1 (P1) and protamine 2 (P2) genes in a population of infertile men with protamine deregulation, men presenting for infertility work-up with normal protamine ratios, and a population of unrelated, fertile men from the Utah Genetic Reference Project (UGRP). This analysis has identified 14 single nucleotide polymorphisms (SNPs), of which 13 were novel SNPs in the UTRs of P1 and P2, and verified the existence of a variable length repeat (VLR), GA n , in the P2 5 0 region. The SNP frequencies and VLR allelic frequencies did not achieve statistical significance between the populations, however, one of the SNPs identified in the 3 0 UTR of protamine 2 was found at a low frequency in the abnormal protamine patients, but was completely absent in men with verified normal protamine ratio and donors of known fertility.In conclusion, a number of SNPs have been reported in the protamine genes and the untranslated regions, however, these gene variants do not appear to be responsible for protamine deficiency. Hence, the underlying cause for aberrant protamine expression may possibly be due to abnormalities in candidate spermatogenic transcriptional=translational regulators, post-translational modifiers, or as-of-yet unidentified factors affecting the testicular environment.

show abstract

Section: Introductionmentioning

confidence: 99%

Identification of Genetic Variation in the 5′ and 3′ Non-coding Regions of the Protamine Genes in Patients with Protamine Deregulation

Hammoud

Emery

Aoki

et al. 2007

Archives of Andrology

View full text Add to dashboard Cite

show abstract

“…Testis-specific variants of histones, transitional proteins, and finally protamines replace somatic histones as the DNA condenses (1,2). The complement of spermatogenic histones changes during differentiation, and this process has been described in detail for rodents (1).…”

mentioning

confidence: 99%

Human Testis/Sperm-specific Histone H2B (hTSH2B)

Zalensky

Siino

Gineitis

et al. 2002

Journal of Biological Chemistry

130

104

View full text Add to dashboard Cite

Human sperm, unlike the sperm of other mammals, contain replacement histones with unknown biological functions. Here, we report the identification of the novel human gene coding for a testis/sperm-specific histone H2B (hTSH2B). This variant histone is 85% homologous to somatic H2B and has over 93% homology with the testis H2B of rodents. Using genomic PCR, two genetic alleles of hTSH2B were found in the human population. The hTSH2B gene is transcribed exclusively in testis, and the corresponding protein is also present in mature sperm. We expressed recombinant hTSH2B and identified this protein with a particular H2B subtype expressed in vivo. The subnuclear distribution of H2B variants in sperm was determined using biochemical fractionation and immunoblotting. The H2B variant associated with telomere-binding activity (15) was solubilized by Triton X-100 or micrococcal nuclease extraction, whereas hTSH2B was relatively tightly bound in nuclei. Immunofluorescence showed that hTSH2B was concentrated in spots located at the basal nuclear area of a subpopulation (20% of cells) of mature sperm. This fact may be of particular importance, because the hTSH2B "positive" and "negative" sperm cells may undergo significantly different decondensation processes following fertilization.During mammalian spermatogenesis, chromatin undergoes stage-specific structural reorganization. Testis-specific variants of histones, transitional proteins, and finally protamines replace somatic histones as the DNA condenses (1, 2). The complement of spermatogenic histones changes during differentiation, and this process has been described in detail for rodents (1). Whereas some testis histones (TH) 1 appear in the early stages of spermatogenesis for instance in spermatogonia (3) and some appear at late stages (e.g. in spermatids (4, 5)), the majority of TH are synthesized and incorporated into chromatin during meiosis (6). Rodent testis histones are replacement subtypes that differ in primary structure from the major somatic variants (3-5, 7-9). Although it is generally assumed that histone variants of germ line cells contribute to the restructuring of chromatin during spermatogenesis, their specific biological functions remain to be established.In contrast to other mammals, mature human sperm retains a set of core histones representing 10 -15% of basic proteins (10 -12). Of these, histone H2B fraction (hSH2B) is the most abundant (10, 13). A complex composition of the hSH2B has been indicated (12). Although 17 replication-dependent H2B genes have been identified so far in the human genome (14), this complement contains neither testis-nor sperm-specific genes. We were particularly interested in the characterization of sperm H2B because of our recent finding that a H2B-related protein is an essential part of the telomere-binding complex in human sperm (15).In this paper, the hSH2B group has been characterized using a combination of biochemical and immunochemical techniques. Further, a gene for a novel human histone H2B variant belonging to thi...

show abstract

“…Subsequently, histones are replaced by transition proteins tP1-4, which are gradually replaced by the small, 50 amino-acids long, and highly basic, arginine rich protamines P1 and P2. extreme nuclear and DNA condensation is then achieved in the sperm, presumably due to compact alignment of adjacent DNA strands to perform sheet-like arrangement with strong anchoring of the protamines by disulphide bridges (46). this type of crystallinelike structure, sixfold more compact than metaphase chromosomes underlies the heavy transcriptional inertness of mature spermatozoa.…”

Section: Nuclear Modifications During Gametogenesismentioning

confidence: 99%