scholarly journals Tissue-Specific Trans Regulation of the Mouse Epigenome

Genetics ◽  
2018 ◽  
Vol 211 (3) ◽  
pp. 831-845 ◽  
Author(s):  
Christopher L. Baker ◽  
Michael Walker ◽  
Seda Arat ◽  
Guruprasad Ananda ◽  
Pavlina Petkova ◽  
...  
Keyword(s):  
Germ Cells ◽  
Recombinant Inbred Lines ◽  
Embryonic Stem ◽  
Cell Types ◽  
Epigenetic Landscape ◽  
Dna Double Strand Breaks ◽  
Male Germ Cells ◽  
Tissue Specific ◽  
Natural Genetic Variation ◽  
Regulatory Loci

The epigenetic landscape varies greatly among cell types. Although a variety of writers, readers, and erasers of epigenetic features are known, we have little information about the underlying regulatory systems controlling the establishment and maintenance of these features. Here, we have explored how natural genetic variation affects the epigenome in mice. Studying levels of H3K4me3, a histone modification at sites such as promoters, enhancers, and recombination hotspots, we found tissue-specific trans-regulation of H3K4me3 levels in four highly diverse cell types: male germ cells, embryonic stem cells, hepatocytes, and cardiomyocytes. To identify the genetic loci involved, we measured H3K4me3 levels in male germ cells in a mapping population of 59 BXD recombinant inbred lines. We found extensive trans-regulation of H3K4me3 peaks, including six major histone quantitative trait loci (QTL). These chromatin regulatory loci act dominantly to suppress H3K4me3, which at hotspots reduces the likelihood of subsequent DNA double-strand breaks. QTL locations do not correspond with genes encoding enzymes known to metabolize chromatin features. Instead their locations match clusters of zinc finger genes, making these possible candidates that explain the dominant suppression of H3K4me3. Collectively, these data describe an extensive, set of chromatin regulatory loci that control the epigenetic landscape.

scholarly journals Tissue-specific trans regulation of the mouse epigenome

2018 ◽  
Author(s):  
Christopher L. Baker ◽  
Michael Walker ◽  
Seda Arat ◽  
Guruprasad Ananda ◽  
Pavlina Petkova ◽  
...  
Keyword(s):  
Germ Cells ◽  
Es Cells ◽  
Recombinant Inbred Lines ◽  
Embryonic Stem ◽  
Cell Types ◽  
Dna Double Strand Breaks ◽  
Male Germ Cells ◽  
Tissue Specific ◽  
Natural Genetic Variation ◽  
Regulatory Loci

ABSTRACTAlthough a variety of writers, readers, and erasers of epigenetic modifications are known, we have little information about the underlying regulatory systems controlling the establishment and maintenance of the epigenetic landscape, which varies greatly among cell types. Here, we have explored how natural genetic variation impacts the epigenome in mice. Studying levels of H3K4me3, a histone modification at sites such as promoters, enhancers, and recombination hotspots, we found tissue-specific trans-regulation of H3K4me3 levels in four highly diverse cell types: male germ cells, embryonic stem (ES) cells, hepatocytes and cardiomyocytes. To identify the genetic loci involved, we measured H3K4me3 levels in male germ cells in a mapping population of 60 BXD recombinant inbred lines, identifying extensive trans-regulation primarily controlled by six major histone quantitative trait loci (hQTL). These chromatin regulatory loci act dominantly to suppress H3K4me3, which at hotspots reduces the likelihood of subsequent DNA double-strand breaks. QTL locations do not correspond with enzyme known to metabolize chromatin features. Instead their locations match clusters of zinc finger genes, making these possible candidates that explain the dominant suppression of H3K4me3. Collectively, these data describe an extensive, tissue-specific set of chromatin regulatory loci that control functionally related chromatin sites.

scholarly journals Parp3 promotes long-range end joining in murine cells

2018 ◽  
Vol 115 (40) ◽  
pp. 10076-10081 ◽  
Author(s):  
Jacob V. Layer ◽  
J. Patrick Cleary ◽  
Alexander J. Brown ◽  
Kristen E. Stevenson ◽  
Sara N. Morrow ◽  
...  
Keyword(s):  
Chromosomal Rearrangements ◽  
Embryonic Stem ◽  
Cell Types ◽  
Strand Break ◽  
Nonhomologous End Joining ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Strand Breaks ◽  
Class Switch

Chromosomal rearrangements, including translocations, are early and essential events in the formation of many tumors. Previous studies that defined the genetic requirements for rearrangement formation have identified differences between murine and human cells, most notably in the role of classic and alternative nonhomologous end-joining (NHEJ) factors. We reported that poly(ADP)ribose polymerase 3 (PARP3) promotes chromosomal rearrangements induced by endonucleases in multiple human cell types. We show here that in contrast to classic (c-NHEJ) factors, Parp3 also promotes rearrangements in murine cells, including translocations in murine embryonic stem cells (mESCs), class–switch recombination in primary B cells, and inversions in tail fibroblasts that generateEml4–Alkfusions. In mESCs, Parp3-deficient cells had shorter deletion lengths at translocation junctions. This was corroborated using next-generation sequencing ofEml4–Alkjunctions in tail fibroblasts and is consistent with a role for Parp3 in promoting the processing of DNA double-strand breaks. We confirmed a previous report that Parp1 also promotes rearrangement formation. In contrast with Parp3, rearrangement junctions in the absence of Parp1 had longer deletion lengths, suggesting that Parp1 may suppress double-strand break processing. Together, these data indicate that Parp3 and Parp1 promote rearrangements with distinct phenotypes.

scholarly journals THE USE OF SEMIPERMEABLE SPHERES ENGULFED WITH MOUSE EMBRYONIC STEM CELLS TO GENERATE MALE GERM CELLS

2020 ◽  
Vol 114 (3) ◽  
pp. e439
Author(s):  
Sherina Lawrence ◽  
Mounia Haddad ◽  
Philip Xie ◽  
Zev Rosenwaks ◽  
Gianpiero D. Palermo
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Germ Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Male Germ Cells

Nanos2 promotes differentiation of chicken (Gallus gallus ) embryonic stem cells to male germ cells

2018 ◽  
Vol 119 (6) ◽  
pp. 4435-4446 ◽  
Author(s):  
Wenhui Zhang ◽  
Yulin Bi ◽  
Yingjie Wang ◽  
Dong Li ◽  
Nana He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Germ Cells ◽  
Embryonic Stem ◽  
Gallus Gallus ◽  
Male Germ Cells

scholarly journals Rho family GTPase Rnd2 interacts and co-localizes with MgcRacGAP in male germ cells

2003 ◽  
Vol 372 (1) ◽  
pp. 105-112 ◽  
Author(s):  
Nathalie NAUD ◽  
Aminata TOURÉ ◽  
Jianfeng LIU ◽  
Charles PINEAU ◽  
Laurence MORIN ◽  
...  
Keyword(s):  
Germ Cells ◽  
In Vitro Model ◽  
Cell Types ◽  
Glutathione S Transferase ◽  
Rac Gtpase ◽  
Male Germ Cells ◽  
Rho Family ◽  
Vitro Model ◽  
Null Mutant Mice

The male-germ-cell Rac GTPase-activating protein gene (MgcRacGAP) was initially described as a human RhoGAP gene highly expressed in male germ cells at spermatocyte stage, but exhibits significant levels of expression in most cell types. In somatic cells, MgcRacGAP protein was found to both concentrate in the midzone/midbody and be required for cytokinesis. As a RhoGAP, MgcRacGAP has been proposed to down-regulate RhoA, which is localized to the cleavage furrow and midbody during cytokinesis. Due to embryonic lethality in MgcRacGAP-null mutant mice and to the lack of an in vitro model of spermatogenesis, nothing is known regarding the role and mode of action of MgcRacGAP in male germ cells. We have analysed the expression, subcellular localization and molecular interactions of MgcRacGAP in male germ cells. Whereas MgcRacGAP was found only in spermatocytes and early spermatids, the widespread RhoGTPases RhoA, Rac1 and Cdc42 (which are, to various extents, in vitro substrates for MgcRacGAP activity) were, surprisingly, not detected at these stages. In contrast, Rnd2, a Rho family GTPase-deficient G-protein was found to be co-expressed with MgcRacGAP in spermatocytes and spermatids. MgcRacGAP was detected in the midzone of meiotic cells, but also, unexpectedly, in the Golgi-derived pro-acrosomal vesicle, co-localizing with Rnd2. In addition, a stable Rnd2–MgcRacGAP molecular complex could be evidenced by glutathione S-transferase pull-down and co-immunoprecipitation experiments. We conclude that Rnd2 is a probable physiological partner of MgcRacGAP in male germ cells and we propose that MgcRacGAP, and, quite possibly, other RhoGAPs, may participate in signalling pathways involving Rnd family proteins.

Generation of progeny from embryonic stem cells by microinsemination of male germ cells from chimeric mice

genesis ◽  
2005 ◽  
Vol 43 (1) ◽  
pp. 34-42 ◽  
Author(s):  
Eiji Mizutani ◽  
Hiroshi Ohta ◽  
Satoshi Kishigami ◽  
Nguyen Van Thuan ◽  
Takafusa Hikichi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Germ Cells ◽  
Embryonic Stem ◽  
Chimeric Mice ◽  
Male Germ Cells

scholarly journals Germline competent mesoderm: the substrate for vertebrate germline and somatic stem cells?

Biology Open ◽  
2021 ◽  
Vol 10 (10) ◽  
Author(s):  
Aaron M. Savage ◽  
Ramiro Alberio ◽  
Andrew D. Johnson
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Germ Cells ◽  
Molecular Mechanisms ◽  
Germ Plasm ◽  
Cell Types ◽  
Model Organisms ◽  
Developmental Potential ◽  
Tissue Specific ◽  
Tissue Specific Stem Cells

ABSTRACT In vitro production of tissue-specific stem cells [e.g. haematopoietic stem cells (HSCs)] is a key goal of regenerative medicine. However, recent efforts to produce fully functional tissue-specific stem cells have fallen short. One possible cause of shortcomings may be that model organisms used to characterize basic vertebrate embryology (Xenopus, zebrafish, chick) may employ molecular mechanisms for stem cell specification that are not conserved in humans, a prominent example being the specification of primordial germ cells (PGCs). Germ plasm irreversibly specifies PGCs in many models; however, it is not conserved in humans, which produce PGCs from tissue termed germline-competent mesoderm (GLCM). GLCM is not conserved in organisms containing germ plasm, or even in mice, but understanding its developmental potential could unlock successful production of other stem cell types. GLCM was first discovered in embryos from the axolotl and its conservation has since been demonstrated in pigs, which develop from a flat-disc embryo like humans. Together these findings suggest that GLCM is a conserved basal trait of vertebrate embryos. Moreover, the immortal nature of germ cells suggests that immortality is retained during GLCM specification; here we suggest that the demonstrated pluripotency of GLCM accounts for retention of immortality in somatic stem cell types as well. This article has an associated Future Leaders to Watch interview with the author of the paper.

scholarly journals SETDB1 plays an essential role in maintenance of gonocyte survival in pigs

Reproduction ◽  
2017 ◽  
Vol 154 (1) ◽  
pp. 23-34 ◽  
Author(s):  
Tiantian Liu ◽  
Pengfei Zhang ◽  
Tianjiao Li ◽  
Xiaoxu Chen ◽  
Zhenshuo Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Germ Cells ◽  
Theoretical Basis ◽  
Histone H3 ◽  
Embryonic Stem ◽  
Male Germ Cells ◽  
Heterochromatin Formation ◽  
Epigenetic Regulator ◽  
And Function

Histone methyltransferase SETDB1 suppresses gene expression and modulates heterochromatin formation through H3K9me2/3. Previous studies have revealed that SETDB1 catalyzes lysine 9 of histone H3 tri-methylation and plays essential roles in maintaining the survival of embryonic stem cells and spermatogonial stem cells in mice. However, the function of SETDB1 in porcine male germ cells remains unclear. The aim of the present study was to reveal the expression profile and function of SETDB1 in porcine germ cells. SETDB1 expression gradually increased during testis development. SETDB1 was strongly localized in gonocytes. Knockdown of SETDB1 gene expression led to gonocyte apoptosis and a decrease in H3K27me3, but no significant change in H3K9me3. These observations suggested that SETDB1 is a novel epigenetic regulator of porcine male germ cells, and contributes to the maintenance of gonocyte survival in pigs, probably due to the regulation of H3K27me3 rather than H3K9me3. These findings will provide a theoretical basis for the future study of epigenetic regulation of spermatogenesis.

Regulation of Hedgehog Signaling in Chicken Embryonic Stem Cells Differentiation Into Male Germ Cells (Gallus )

2016 ◽  
Vol 118 (6) ◽  
pp. 1379-1386 ◽  
Author(s):  
Hao Chen ◽  
Qisheng Zuo ◽  
Yinjie Wang ◽  
Mahmoud F. Ahmed ◽  
Kai Jin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Germ Cells ◽  
Hedgehog Signaling ◽  
Embryonic Stem ◽  
Male Germ Cells ◽  
Chicken Embryonic Stem Cells
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