Combined proteomic and<i>in silico</i>approaches to decipher post-meiotic male genome reprogramming in mice

Rousseaux, Sophie; Khochbin, Saadi

doi:10.3109/19396368.2012.663055

Cited by 13 publications

(10 citation statements)

References 43 publications

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“…Together with proteomic and in silico approaches, these investigations have yielded significant progress in our understanding of postmeiotic reprogramming of the male genome in mammals (reviewed e.g. in [38]) and important principles underlying the selective retention of histones during spermiogenesis are beginning to emerge [13]. Most of these mechanistic insights were gained by comparison of well characterized patterns of known gene expression in the embryo and in spermatogenic cells with the patterning of sperm histone retention.…”

Section: Discussionmentioning

confidence: 99%

Paternal Poly (ADP-ribose) Metabolism Modulates Retention of Inheritable Sperm Histones and Early Embryonic Gene Expression

et al. 2014

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To achieve the extreme nuclear condensation necessary for sperm function, most histones are replaced with protamines during spermiogenesis in mammals. Mature sperm retain only a small fraction of nucleosomes, which are, in part, enriched on gene regulatory sequences, and recent findings suggest that these retained histones provide epigenetic information that regulates expression of a subset of genes involved in embryo development after fertilization. We addressed this tantalizing hypothesis by analyzing two mouse models exhibiting abnormal histone positioning in mature sperm due to impaired poly(ADP-ribose) (PAR) metabolism during spermiogenesis and identified altered sperm histone retention in specific gene loci genome-wide using MNase digestion-based enrichment of mononucleosomal DNA. We then set out to determine the extent to which expression of these genes was altered in embryos generated with these sperm. For control sperm, most genes showed some degree of histone association, unexpectedly suggesting that histone retention in sperm genes is not an all-or-none phenomenon and that a small number of histones may remain associated with genes throughout the genome. The amount of retained histones, however, was altered in many loci when PAR metabolism was impaired. To ascertain whether sperm histone association and embryonic gene expression are linked, the transcriptome of individual 2-cell embryos derived from such sperm was determined using microarrays and RNA sequencing. Strikingly, a moderate but statistically significant portion of the genes that were differentially expressed in these embryos also showed different histone retention in the corresponding gene loci in sperm of their fathers. These findings provide new evidence for the existence of a linkage between sperm histone retention and gene expression in the embryo.

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Section: Discussionmentioning

confidence: 99%

Paternal Poly (ADP-ribose) Metabolism Modulates Retention of Inheritable Sperm Histones and Early Embryonic Gene Expression

et al. 2014

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“…The absence of expression, or even an increase or decrease, of some spermatozoa proteins can lead to abnormal morphology, altered or poor motility and fertilization failures (for a review see 4 ). The molecular basis of this post-testicular maturation remained unexplored for decades 5 . However, in recent years proteomics has made a substantial contribution to the understanding of sperm epididymal maturation 6 7 3 2 .…”

Section: Introductionmentioning

confidence: 99%

Human Spermatozoa as a Model for Detecting Missing Proteins in the Context of the Chromosome-Centric Human Proteome Project

et al. 2015

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The Chromosome-Centric Human Proteome Project (C-HPP) aims at cataloguing the proteins as gene products encoded by the human genome in a chromosome-centric manner. The existence of products of about 82% of the genes has been confirmed at the protein level. However, the number of so-called "missing proteins" remains significant. It was recently suggested that the expression of proteins that have been systematically missed might be restricted to particular organs or cell types, for example, the testis. Testicular function, and spermatogenesis in particular, is conditioned by the successive activation or repression of thousands of genes and proteins including numerous germ cell- and testis-specific products. Both the testis and postmeiotic germ cells are thus promising sites at which to search for missing proteins, and ejaculated spermatozoa are a potential source of proteins whose expression is restricted to the germ cell lineage. A trans-chromosome-based data analysis was performed to catalog missing proteins in total protein extracts from isolated human spermatozoa. We have identified and manually validated peptide matches to 89 missing proteins in human spermatozoa. In addition, we carefully validated three proteins that were scored as uncertain in the latest neXtProt release (09.19.2014). A focus was then given to the 12 missing proteins encoded on chromosomes 2 and 14, some of which may putatively play roles in ciliation and flagellum mechanistics. The expression pattern of C2orf57 and TEX37 was confirmed in the adult testis by immunohistochemistry. On the basis of transcript expression during human spermatogenesis, we further consider the potential for discovering additional missing proteins in the testicular postmeiotic germ cell lineage and in ejaculated spermatozoa. This project was conducted as part of the C-HPP initiatives on chromosomes 14 (France) and 2 (Switzerland). The mass spectrometry proteomics data have been deposited with the ProteomeXchange Consortium under the data set identifier PXD002367.

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“…Recent data indicate that non-histone proteins including RNA polymerase III, topoisomerase II ␣, heterochromatin protein 1, and high-mobility group nucleosome-binding proteins (HMGNs) critically influence chromatin structural dynamics (29 -33), but current data are insufficient to fully establish the role played by chromatin-associated proteins in the control of the host cell cycle. Data describing the chromatin-associated proteome (chromatome) during cell division have been reported for C. Elegans (34), yeast (35), and human cells (36), whereas other investigators have carried out proteomic analyses of the DNA damage response complex (37) and postmeiotic genome in mice (38). However, detailed profiling of chromatome dynamics during cell cycle progression has not previously been conducted.…”

mentioning

confidence: 99%

Profiling of the Chromatin-associated Proteome Identifies HP1BP3 as a Novel Regulator of Cell Cycle Progression

Dutta

Ren

Hao

et al. 2014

Molecular & Cellular Proteomics

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The chromatin-associated proteome (chromatome) regulates cellular gene expression by restricting access of transcriptional machinery to template DNA, and dynamic re-modeling of chromatin structure is required to regulate critical cell functions including growth and replication, DNA repair and recombination, and oncogenic transformation in progression to cancer. Central to the control of these processes is efficient regulation of the host cell cycle, which is maintained by rapid changes in chromatin conformation during normal cycle progression. A global overview of chromatin protein organization is therefore essential to fully understand cell cycle regulation, but the influence of the chromatome and chromatin binding topology on host cell cycle progression remains poorly defined. Here we used partial MNase digestion together with iTRAQ-based high-throughput quantitative proteomics to quantify chromatin-associated proteins during interphase progression. We identified a total of 481 proteins with high confidence that were involved in chromatin-dependent events including transcriptional regulation, chromatin reorganization, and DNA replication and repair, whereas the quantitative data revealed the temporal interactions of these proteins with chromatin during interphase progression. When combined with biochemical and functional assays, these data revealed a strikingly dynamic association of protein HP1BP3 with the chromatin complex during different stages of interphase, and uncovered a novel regulatory role for this molecule in transcriptional regulation. We report that HP1BP3 protein maintains heterochromatin integrity during G 1-S progression and regulates the duration of G 1 phase to critically influence cell proliferative capacity. Molecular & Cellular

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Combined proteomic andin silicoapproaches to decipher post-meiotic male genome reprogramming in mice

Cited by 13 publications

References 43 publications

Paternal Poly (ADP-ribose) Metabolism Modulates Retention of Inheritable Sperm Histones and Early Embryonic Gene Expression

Paternal Poly (ADP-ribose) Metabolism Modulates Retention of Inheritable Sperm Histones and Early Embryonic Gene Expression

Human Spermatozoa as a Model for Detecting Missing Proteins in the Context of the Chromosome-Centric Human Proteome Project

Profiling of the Chromatin-associated Proteome Identifies HP1BP3 as a Novel Regulator of Cell Cycle Progression

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