Presence of histone H3 acetylated at lysine 9 in male germ cells and its distribution pattern in the genome of human spermatozoa

Steilmann, C.; Paradowska, Agnieszka; Bartkuhn, Marek; Vieweg, Markus; Schuppe, Hans‐Christian; Bergmann, Martin; Kliesch, Sabine; Weidner, W.; Steger, Klaus

doi:10.1071/rd10197

Cited by 46 publications

(41 citation statements)

References 72 publications

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“…These data may provide insights into the mechanisms by which␣-tubulin isoforms are acetylated and how this impacts the regulation of sperm motility. The site-specific lysine acetylation of histones is known to regulate genomic histone reten- tion (55), transfer of epigenetic information to the oocyte (56), and vertical transfer of epigenetic markers (57). Although acetylation of H4K8, H3K9, H4K12, and H4K16 has been detected in human sperm, there have been no global studies of histone (or other protein) lysine acetylation sites in mature human sperm.…”

Section: Discussionmentioning

confidence: 99%

Acetylproteomic Analysis Reveals Functional Implications of Lysine Acetylation in Human Spermatozoa (sperm)

Diao

Wang

et al. 2015

Molecular & Cellular Proteomics

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Male infertility is a medical condition that has been on the rise globally. Lysine acetylation of human sperm, an essential posttranslational modification involved in the etiology of sperm abnormality, is not fully understood. Therefore, we first generated a qualified pan-anti-acetyllysine monoclonal antibody to characterize the global lysine acetylation of uncapacitated normal human sperm with a proteomics approach. With high enrichment ratios that were up to 31%, 973 lysine-acetylated sites that matched to 456 human sperm proteins, including 671 novel lysine acetylation sites and 205 novel lysine-acetylated proteins, were identified. These proteins exhibited conserved motifs XXXKYXXX, XXXKFXXX, and XXXKHXXX, were annotated to function in multiple metabolic processes, and were localized predominantly in the mitochondrion and cytoplasmic fractions. Between the uncapacitated and capacitated sperm, different acetylation profiles in regard to functional proteins involved in sperm capacitation, sperm-egg recognition, sperm-egg plasma fusion, and fertilization were observed, indicating that acetylation of functional proteins may be required during sperm capacitation. Bioinformatics analysis revealed association of acetylated proteins with diseases and drugs. Novel acetylation of voltage-dependent anion channel proteins was also found. With clinical sperm samples, we observed differed lysine acetyltransferases and lysine deacetylases expression between normal sperm and abnormal sperm of asthenospermia or necrospermia. Furthermore, with sperm samples impaired by epigallocatechin gallate to mimic asthenospermia, we observed that inhibition of sperm motility was partly through the blockade of voltage-dependent anion channel 2 Lys-74 acetylation combined with reduced ATP levels and mitochondrial membrane potential. Taken together, we obtained a qualified pananti-acetyllysine monoclonal antibody, analyzed the acetylproteome of uncapacitated human sperm, and revealed associations between functional protein acetylation and sperm functions. Molecular & Cellular

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Section: Discussionmentioning

confidence: 99%

Acetylproteomic Analysis Reveals Functional Implications of Lysine Acetylation in Human Spermatozoa (sperm)

Diao

Wang

et al. 2015

Molecular & Cellular Proteomics

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“…In preliminary studies with subfertile patients presenting aberrant chromatin condensation as assessed by aniline staining, we found a global reduction of H3K9ac marked sites. 13 However, mRNA profiling has not been yet studied in these individuals, although our studies related to epigenetic modifications of bromodomain testis-specific protein (BRDT) in spermatozoa indicate reduced enrichment of methylated histones and increased mRNA level of BRDT in subfertile patients. 25 Data were compared with the clinical outcomes of patients that correlated barely in aniline blue staining and sperm morphology.…”

Section: Methodsmentioning

confidence: 99%

“…ChIP procedure was performed as previously described by Steilmann et al 13 In this study we used polyclonal IgG ChIP grade (ab46540, Abcam) as a negative control and antibodies against unmodified histone H3 (ab1791, Abcam) as a positive control. 10% of sonicated chromatin (100 μl) was saved for each sample to determine the input chromatin amount.…”

Section: Methodsmentioning

confidence: 99%

“…Comparing data from promoter array with anti-H4K12ac with data of anti-H3K9ac CHIP-on-chip ENCODE array in fertile donors, 13 co-localization of binding sites for anti-H4K12ac and anti-H3K9ac could be demonstrated for nine gene promoters that are involved in reproductive processes and embryonic development, e.g., AFF4 (AF4/ FMR2 family, member 4), AXIN1, NCOA6 (nuclear receptor coactivator 6), OR52A1 (olfactory receptor, family 52, subfamily A, member 1). To compare our H4K12ac data set with H3K27me3 and H3K4me3 we used pre-compiled peak list from Hammoud et al 14 Peaks with promoter occupancy have been extracted from Chip-seq reads.…”

Section: Introductionmentioning

confidence: 99%

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Genome wide identification of promoter binding sites for H4K12ac in human sperm and its relevance for early embryonic development

et al. 2012

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Sperm chromatin reveals two characteristic features in that protamines are the predominant nuclear proteins and remaining histones are highly acetylated. histone h4 acetylated at lysine 12 (h4K12ac) is localized in the post-acrosomal region, while protamine-1 is present within the whole nucleus. chromatin immunoprecipitation in combination with promoter array analysis allowed genome-wide identification of h4K12ac binding sites. previously, we reported enrichment of h4K12ac at cTcF binding sites and promoters of genes involved in developmental processes. here, we demonstrate that h4K12ac is enriched predominantly between ± 2 kb from the transcription start site. In addition, we identified developmentally relevant h4K12ac-associated promoters with high expression levels of their transcripts stored in mature sperm. The highest expressed mRNa codes for testis-specific phD finger protein-7 (phF7), suggesting an activating role of h4K12ac in the regulatory elements of this gene. h4K12ac-associated genes revealed a weak correlation with genes expressed at 4-cell stage human embryos, while 23 h4K12ac-associated genes were activated in 8-cell embryo and 39 in the blastocyst. Genes activated in 4-cell embryos are involved in gene expression, histone fold and DNadependent transcription, while genes expressed in the blastocyst were classified as involved in developmental processes. Immunofluorescence staining detected h4K12ac from the murine male pronucleus to early stages of embryogenesis. aberrant histone acetylation within developmentally important gene promoters in infertile men may reflect insufficient sperm chromatin compaction, which may result in inappropriate transfer of epigenetic information to the oocyte.

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“…In addition to H2B, H3 and its replacement variant H3.3 have been demonstrated to be associated with gene activation (Mito et al 2005). Specific PTMs in H3 are localized in the regions of sperm genome that are active during spermatogenesis and early embryonic development (Brykczynska et al 2010, Steilmann et al 2011. Lastly, H4 is associated with the success of chromatin remodeling during spermatogenesis (Kleiman et al 2008) and male inheritance of chromosomal architecture during zygote development (van der Heijden et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Molecular morphology and function of bull spermatozoa linked to histones and associated with fertility

et al. 2013

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Sub-par fertility in bulls is influenced by alterations in sperm chromatin, and it might not be solved with increased sperm concentration in artificial insemination. Appropriate histone retention during sperm chromatin condensation plays critical roles in male fertility. The objective of this study was to determine failures of sperm chromatin condensation associated with abnormal persistence or accessibility of histones by aniline blue (ANBL) test, expression levels, and cellular localizations of one variant and two core histones (H3.3, H2B, and H4 respectively) in the spermatozoa of low-fertility (LF) vs high-fertility (HF) bulls. The expression levels and cellular localizations of histones in spermatozoa were studied using immunoblotting, immunocytochemistry, and staining methods. The bioinformatics focused on the sequence identity and evolutionary distance of these proteins among three mammalian species: bovine, mouse, and human. We demonstrated that ANBL staining was different within the LF (1.73 (0.55, 0.19)) and HF (0.67 (0.17, 0.06)) groups (P!0.0001), which was also negatively correlated with in vivo bull fertility (rZK0.90, P!0.0001). Although these histones were consistently detectable and specifically localized in bull sperm cells, they were not different between the two groups. Except H2B variants, H3.3 and H4 showed 100% identity and were evolutionarily conserved in bulls, mice and humans. The H2B variants were more conserved between bulls and humans, than in mice. In conclusion, we showed that H2B, H3.3, and H4 were detectable in bull spermatozoa and that sperm chromatin condensation status, changed by histone retention, is related to bull fertility.

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Presence of histone H3 acetylated at lysine 9 in male germ cells and its distribution pattern in the genome of human spermatozoa

Cited by 46 publications

References 72 publications

Acetylproteomic Analysis Reveals Functional Implications of Lysine Acetylation in Human Spermatozoa (sperm)

Acetylproteomic Analysis Reveals Functional Implications of Lysine Acetylation in Human Spermatozoa (sperm)

Genome wide identification of promoter binding sites for H4K12ac in human sperm and its relevance for early embryonic development

Molecular morphology and function of bull spermatozoa linked to histones and associated with fertility

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