DNA methylation and gene expression dynamics during spermatogonial stem cell differentiation in the early postnatal mouse testis

Kubo, Naoki; Toh, Y.; Shirane, Kenjiro; Shirakawa, Takayuki; Kobayashi, Hisato; Sato, Tetsuya; Sone, Hirohito; Sato, Yasuyuki; Tomizawa, Shin-ichi; Tsurusaki, Yoshinori; Shibata, Hiroki; Saitsu, Hirotomo; Suzuki, Yutaka; Matsumoto, Naomichi; Suyama, Mikita; Kono, Toru; Ohbo, Kazuyuki; Sasaki, Hidetada

doi:10.1186/s12864-015-1833-5

Cited by 124 publications

(145 citation statements)

References 79 publications

(132 reference statements)

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“…However, these genes/loci attain their full/expected imprinting prior to puberty. In contrast, the high-OCT4/ ID4 subtypes displayed expected paternal imprints throughout postnatal development, supporting recent work in high-OCT4 neonatal SSCs (Kubo et al 2015). Here we note that the subset of THY1 + and KIT + spermatogonia that shows both imprinting defects and mesenchymal-like features may contribute to the pool of spermatogonia that participates in the first wave of gametogenesis (Yoshida et al 2006).…”

Section: Dynamics Of Imprinting In Developing Germline Stem Cellsmentioning

confidence: 48%

Transcription and imprinting dynamics in developing postnatal male germline stem cells

Hammoud

Low

et al. 2015

Genes Dev.

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Postnatal spermatogonial stem cells (SSCs) progress through proliferative and developmental stages to populate the testicular niche prior to productive spermatogenesis. To better understand, we conducted extensive genomic profiling at multiple postnatal stages on subpopulations enriched for particular markers (THY1, KIT, OCT4, ID4, or GFRa1). Overall, our profiles suggest three broad populations of spermatogonia in juveniles: (1) epithelial-like spermatogonia (THY1 + ; high OCT4, ID4, and GFRa1), (2) more abundant mesenchymal-like spermatogonia (THY1 + ; moderate OCT4 and ID4; high mesenchymal markers), and (3) (in older juveniles) abundant spermatogonia committing to gametogenesis (high KIT + ). Epithelial-like spermatogonia displayed the expected imprinting patterns, but, surprisingly, mesenchymal-like spermatogonia lacked imprinting specifically at paternally imprinted loci but fully restored imprinting prior to puberty. Furthermore, mesenchymal-like spermatogonia also displayed developmentally linked DNA demethylation at meiotic genes and also at certain monoallelic neural genes (e.g., protocadherins and olfactory receptors). We also reveal novel candidate receptor-ligand networks involving SSCs and the developing niche. Taken together, neonates/juveniles contain heterogeneous epithelial-like or mesenchymal-like spermatogonial populations, with the latter displaying extensive DNA methylation/chromatin dynamics. We speculate that this plasticity helps SSCs proliferate and migrate within the developing seminiferous tubule, with proper niche interaction and membrane attachment reverting mesenchymal-like spermatogonial subtype cells back to an epithelial-like state with normal imprinting profiles.

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Section: Dynamics Of Imprinting In Developing Germline Stem Cellsmentioning

confidence: 48%

Transcription and imprinting dynamics in developing postnatal male germline stem cells

Hammoud

Low

et al. 2015

Genes Dev.

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“…DNA cytosine modification is a dynamic process catalyzed by specific DNA methyltransferases (DNMTs) that convert cytosine (C) to 5-methylcytosine (abbreviated 5mC or M; Bestor, Laudano, Mattaliano, & Ingram, 1988; Okano, Xie, & Li, 1998), usually within the sequence context of CpG (Bestor et al, 1988; Okano, Bell, Haber, & Li, 1999; Okano et al, 1998) or CpA (Gowher & Jeltsch, 2001; Kubo et al, 2015; Lister et al, 2013, 2009; Ramsahoye et al, 2000; Vlachogiannis et al, 2015). A subset of 5mC may then be oxidized to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) by the ten-eleven translocation (Tet) dioxygenases in three consecutive Fe(II) and α-ketoglutarate-dependent oxidation reactions (He et al, 2011; Ito et al, 2010, 2011; Tahiliani et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Characterization of How DNA Modifications Affect DNA Binding by C2H2 Zinc Finger Proteins

Patel

Hashimoto

Zhang

et al. 2016

Methods in Enzymology

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Much is known about vertebrate DNA methylation and oxidation; however, much less is known about how modified cytosine residues within particular sequences are recognized. Among the known methylated DNA-binding domains, the Cys2-His2 zinc finger (ZnF) protein superfamily is the largest with hundreds of members, each containing tandem ZnFs ranging from 3 to >30 fingers. We have begun to biochemically and structurally characterize these ZnFs not only on their sequence specificity but also on their sensitivity to various DNA modifications. Rather than following published methods of refolding insoluble ZnF arrays, we have expressed and purified soluble forms of ZnFs, ranging in size from a tandem array of two to six ZnFs, from seven different proteins. We also describe a fluorescence polarization assay to measure ZnFs affinity with oligonucleotides containing various modifications and our approaches for cocrystallization of ZnFs with oligonucleotides.

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“…We and others have shown that DNA methylation occurs not only at promoter regions but also at other regulatory regions (Khalid et al, 2014; Kubo et al, 2015; Rea et al, 2017). We therefore asked if these changes in 5hmC occur at other functional genomic regions as well.…”

Section: Resultsmentioning

confidence: 90%

Selective inhibition of CTCF binding by iAs directs TET-mediated reprogramming of 5-hydroxymethylation patterns in iAs-transformed cells

Rea

Gripshover

Fondufe‐Mittendorf

2018

Toxicology and Applied Pharmacology

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Methylation at cytosine (5mC) is a fundamental epigenetic DNA modification recently associated with iAs-mediated carcinogenesis. In contrast, the role of 5-hydroxymethylcytosine (5hmC), the oxidation product of 5mC in iAs-mediated carcinogenesis is unknown. Here we assess the hydroxymethylome in iAs-transformed cells, showing that dynamic modulation of hydroxymethylated DNA is associated with specific transcriptional networks. Moreover, this pathologic iAs-mediated carcinogenesis is characterized by a shift toward a higher hydroxymethylation pattern genome-wide. At specific promoters, hydroxymethylation correlated with increased gene expression. Furthermore, this increase in hydroxymethylation occurs concurrently with an upregulation of ten-eleven translocation (TET) enzymes that oxidize 5-methylcytosine (5mC) in DNA. To gain an understanding into how iAs might impact TET expression, we found that iAs inhibits the binding of CTCF at the proximal, weak CTCF binding sites of the TET1 and TET2 gene promoters and enhances CTCF binding at the stronger distal binding site. Further analyses suggest that this distal site acts as an enhancer, thus high CTCF occupancy at the enhancer region of TET1 and TET2 possibly drives their high expression in iAs-transformed cells. These results have major implications in understanding the impact of differential CTCF binding, genome architecture and its consequences in iAs-mediated pathogenesis.

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DNA methylation and gene expression dynamics during spermatogonial stem cell differentiation in the early postnatal mouse testis

Cited by 124 publications

References 79 publications

Transcription and imprinting dynamics in developing postnatal male germline stem cells

Transcription and imprinting dynamics in developing postnatal male germline stem cells

Characterization of How DNA Modifications Affect DNA Binding by C2H2 Zinc Finger Proteins

Selective inhibition of CTCF binding by iAs directs TET-mediated reprogramming of 5-hydroxymethylation patterns in iAs-transformed cells

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