Linking transcriptomics and proteomics in spermatogenesis

Chalmel, Frédéric; Rolland, Antoine

doi:10.1530/rep-15-0073

Cited by 65 publications

(43 citation statements)

References 66 publications

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“…This regulative scenario also enables RHOXF1 and RHOXF2/2B to maintain some common functions despite major sequence differences and distinct expression pattern. We note that even though RHOXF1 was not detectable after the round spermatid stage (13), its influence may extend beyond this stage, as many mRNAs transcribed in the round spermatid stage are translated and function at later stages (38).…”

mentioning

confidence: 75%

The humanRHOXgene cluster: target genes and functional analysis of gene variants in infertile men

Borgmann

Tüttelmann²,

Dworniczak³

et al. 2016

Hum. Mol. Genet.

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The X-linked reproductive homeobox (RHOX) gene cluster encodes transcription factors preferentially expressed in reproductive tissues. This gene cluster has important roles in male fertility based on phenotypic defects of Rhox-mutant mice and the finding that aberrant RHOX promoter methylation is strongly associated with abnormal human sperm parameters. However, little is known about the molecular mechanism of RHOX function in humans. Using gene expression profiling, we identified genes regulated by members of the human RHOX gene cluster. Some genes were uniquely regulated by RHOXF1 or RHOXF2/2B, while others were regulated by both of these transcription factors. Several of these regulated genes encode we demonstrate how the X-linked RHOX gene cluster may function in normal human spermatogenesis and we provide evidence that it is impaired in human male fertility.

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confidence: 75%

The humanRHOXgene cluster: target genes and functional analysis of gene variants in infertile men

Borgmann

Tüttelmann²,

Dworniczak³

et al. 2016

Hum. Mol. Genet.

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“…Proper expression of these factors is dynamically controlled at transcriptional and post-transcriptional levels (Paronetto and Sette, 2010, Chalmel and Rolland, 2015). Testicular paralogs of core transcriptional components, such as TAF7L (Zhou et al., 2013), or testis-specific transcription factors, such as the cyclic AMP-responsive factor CREM (Nantel and Sassone-Corsi, 1996), together with stage-specific epigenetic modifications (Godmann et al., 2007, Soumillon et al., 2013, Hammoud et al., 2014), contribute to orchestrate gene expression programs during spermatogenesis.…”

Section: Introductionmentioning

confidence: 99%

An Orchestrated Intron Retention Program in Meiosis Controls Timely Usage of Transcripts during Germ Cell Differentiation

et al. 2017

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SummaryGlobal transcriptome reprogramming during spermatogenesis ensures timely expression of factors in each phase of male germ cell differentiation. Spermatocytes and spermatids require particularly extensive reprogramming of gene expression to switch from mitosis to meiosis and to support gamete morphogenesis. Here, we uncovered an extensive alternative splicing program during this transmeiotic differentiation. Notably, intron retention was largely the most enriched pattern, with spermatocytes showing generally higher levels of retention compared with spermatids. Retained introns are characterized by weak splice sites and are enriched in genes with strong relevance for gamete function. Meiotic intron-retaining transcripts (IRTs) were exclusively localized in the nucleus. However, differently from other developmentally regulated IRTs, they are stable RNAs, showing longer half-life than properly spliced transcripts. Strikingly, fate-mapping experiments revealed that IRTs are recruited onto polyribosomes days after synthesis. These studies reveal an unexpected function for regulated intron retention in modulation of the timely expression of select transcripts during spermatogenesis.

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“…The expression of STRA8, DAZL, SYCP3, PRDM9 AND DMC1 indicates the initiation and undergoing of meiosis (5). Spermatogenesis is driven by the stage-specific expression of genes that are regulated transcriptionally and post-transcriptionally (6), and it involves the expression of a large number of highly or specifically expressed coding and non-coding genes in various spermatogenic cells.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators and RNA binding proteins

et al. 2016

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AbstractmiRNAs play important roles during mammalian spermatogenesis. However, the function of most miRNAs in spermatogenesis and the underlying mechanisms remain unknown. Here, we report that miR-202 is highly expressed in mouse spermatogonial stem cells (SSCs), and is oppositely regulated by Glial cell-Derived Neurotrophic Factor (GDNF) and retinoic acid (RA), two key factors for SSC self-renewal and differentiation. We used inducible CRISPR-Cas9 to knockout miR-202 in cultured SSCs, and found that the knockout SSCs initiated premature differentiation accompanied by reduced stem cell activity and increased mitosis and apoptosis. Target genes were identified with iTRAQ-based proteomic analysis and RNA sequencing, and are enriched with cell cycle regulators and RNA-binding proteins. Rbfox2 and Cpeb1 were found to be direct targets of miR-202 and Rbfox2 but not Cpeb1, is essential for the differentiation of SSCs into meiotic cells. Accordingly, an SSC fate-regulatory network composed of signaling molecules of GDNF and RA, miR-202 and diverse downstream effectors has been identified.

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Linking transcriptomics and proteomics in spermatogenesis

Cited by 65 publications

References 66 publications

The humanRHOXgene cluster: target genes and functional analysis of gene variants in infertile men

The humanRHOXgene cluster: target genes and functional analysis of gene variants in infertile men

An Orchestrated Intron Retention Program in Meiosis Controls Timely Usage of Transcripts during Germ Cell Differentiation

MicroRNA-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators and RNA binding proteins

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