Well-defined genome architecture in the human sperm nucleus

Zalensky, Andrei O.; Allen, Michael J.; Kobayashi, Arthur; Zalenskaya, Irina A.; Balhorn, Rod; Bradbury, E. M.

doi:10.1007/bf00357684

Cited by 161 publications

(148 citation statements)

References 43 publications

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“…However, even though sperm chromatin is highly condensed there is evidence that it is also highly organised, with the location of domains that contain particular chromosomal regions being conserved from sperm to sperm (Zalensky et al 1995, Hazzouri et al 2000. Recent work also suggests that regions accessible to exogenously applied endonucleases contain sequences that differ in gene composition from the bulk chromatin.…”

Section: Discussionmentioning

confidence: 99%

Key gene regulatory sequences with distinctive ontological signatures associate with differentially endonuclease-accessible mouse sperm chromatin

Saida

Iles²,

Elnefati³

et al. 2011

Reproduction

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Using a well-established endonuclease-based chromatin dissection procedure in conjunction with both experimental comparative genome hybridisation (CGH) array profiling and in silico data mining, we show that mouse spermatozoa contain chromatin that is sensitive and resistant to digestion with micrococcal nuclease (MNase). Sequences represented in the micrococcal nuclease digestion solubilised (MNDS) but not the MND insoluble (MNDI) chromatin are strongly enriched in chromosomal regions of high gene density. Furthermore, by fluorescence in situ hybridisation (FISH) analysis, we show that MNDS and MNDI DNAs occupy distinct domains of decondensed mouse sperm nuclei that may also retain abundant histones. More detailed in silico analysis of CGH probe location in relation to known promoters and sequences recognised by CCCTC binding factor (CTCF) shows a significant excess of both in MNDS chromatin. A functional analysis of gene promoters reveals strong ontological signatures for ion transport on methylated promoters associated with CTCF binding sequences in MNDS chromatin. Sensory perception is the only strong ontological signature present in MNDI chromatin, driven by promoters that are not associated with CTCF regardless of their methylation status.

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Section: Discussionmentioning

confidence: 99%

Key gene regulatory sequences with distinctive ontological signatures associate with differentially endonuclease-accessible mouse sperm chromatin

Saida

Iles²,

Elnefati³

et al. 2011

Reproduction

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“…During spermiogenesis, nuclear structure undergoes a dramatic reorganization unique to male germ cells that packs the DNA in a specific topology within the sperm nucleus (26,27). How the specificity of this process is achieved is at present not well understood.…”

Section: Discussionmentioning

confidence: 99%

Polar nuclear localization of H1T2, a histone H1 variant, required for spermatid elongation and DNA condensation during spermiogenesis

Martianov

Brancorsini

Catena

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

190

168

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Spermiogenesis entails a major biochemical and morphological restructuring of the germ cell involving replacement of the somatic histones by protamines packing the DNA into the condensed spermatid nucleus and elimination of the cytoplasm during the elongation phase. We describe H1T2, an histone H1 variant selectively and transiently expressed in male haploid germ cells during spermiogenesis. In round and elongating spermatids, H1T2 specifically localizes to a chromatin domain at the apical pole, revealing a polarity in the spermatid nucleus. Inactivation by homologous recombination shows that H1T2 is critical for spermiogenesis as male H1t2 ؊/؊ mice have greatly reduced fertility. Analysis of spermiogenesis in H1t2 mutant mice shows delayed nuclear condensation and aberrant elongation. As a result, mutant spermatids are characterized by the presence of residual cytoplasm, acrosome detachment, and fragmented DNA. Hence, H1T2 is a protein required for proper cell restructuring and DNA condensation during the elongation phase of spermiogenesis.chromatin ͉ mouse ͉ protamine ͉ acrosome M ammalian spermatogenesis involves the differentiation of diploid spermatogonia into spermatocytes and then, through two successive meiotic divisions, into haploid round spermatids. During spermiogenesis, the haploid round spermatids undergo an elongation phase, transforming them into mature spermatozoa. This process entails a major biochemical and morphological restructuring of the germ cell where the majority of the somatic histones are replaced, first by transition proteins, then protamines packing the DNA into the sperm cell nucleus.Differentiating male germ cells use specialized transcriptional regulatory mechanisms involving testis-specific paralogues of transcription factors such as TLF͞TRF2, ALF, and TAF7L (1-3). In addition, male germ cells contain specialized chromatin components such as H1T, a histone H1 variant specifically expressed in pachytene spermatocytes and early haploid cells (4), and HILS1, a histone H1-related protein specifically expressed in elongating and elongated spermatids (5). However, no spermatogenesis abnormalities are observed in mice lacking the H1t gene, perhaps because of redundancy with the somatic H1.1, which is also expressed at this stage (6-9). This finding contrasts with the reduced fertility and defective spermiogenesis in mice lacking transition proteins 1 or 2 or haploinsufficient for protamines 1 or 2 (10-12). Thus, whereas H1 histones have been proposed to play a role in the formation of higher-order chromatin structure, the physiological functions of the tissue-specific variants remain obscure. Here, we describe a male germ cellspecific H1-related protein, H1T2, that plays a critical role during the elongation phase of spermiogenesis. Materials and MethodsCloning and Inactivation of H1t2. The H1t2 cDNA was cloned from a mouse testis cDNA library by screening with the short mouse TEST640 EST probe as described (2, 13). 5Ј RACE using mouse testis RNA was performed to confirm the sequence o...

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“…Similar to somatic cells, individual chromosomes occupydistinct territories (Haaf & Ward 1995, Zalensky et al 1995;…”

Section: Introductionmentioning

confidence: 99%

“…Telomeres are localized at the nuclear periphery where theyinteract in dimers and tetramers (Zalensky et al 1995,Meyer-Ficca et al 1998,Hazzouri et al 2000.…”

Section: Introductionmentioning

confidence: 99%

Non-random positioning of chromosomes in human sperm nuclei

2004

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In human spermatozoa, the arrangement of chromosomes is non-random. Characteristic features are association of centromeres in the interior chromocenter and peripheral location of telomeres. In this paper, we have investigated the highest level of order in DNA packing in sperm ^ absolute and relative intranuclear chromosome positioning. Asymmetrical nuclear shape, existence of a defined spatial marker, and the haploid complement of chromosomes facilitated an experimental approach using in situ hybridization. Our results showed the tendencyfor non-random intranuclear location of individual chromosome territories. Moreover, centromeres demonstrated specific intranuclear position, and were located within a limited area of nuclear volume. Additionally, the relative positions of centromeres were non-random; some were found in close proximity, while other pairs showed significantly greater intercentromere distances. Therefore, a unique and specific adherence mayexist between chromosomes in sperm. The observed chromosome order is discussed in relation to sperm nuclei decondensation, and reactivation during fertilization.

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Well-defined genome architecture in the human sperm nucleus

Cited by 161 publications

References 43 publications

Key gene regulatory sequences with distinctive ontological signatures associate with differentially endonuclease-accessible mouse sperm chromatin

Key gene regulatory sequences with distinctive ontological signatures associate with differentially endonuclease-accessible mouse sperm chromatin

Polar nuclear localization of H1T2, a histone H1 variant, required for spermatid elongation and DNA condensation during spermiogenesis

Non-random positioning of chromosomes in human sperm nuclei

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