MLL2 Is Required in Oocytes for Bulk Histone 3 Lysine 4 Trimethylation and Transcriptional Silencing

Andreu-Vieyra, Claudia; Chen, Ruihong; Agno, Julio E.; Glaser, Stefan; Anastassiadis, Konstantinos; Stewart, A. Francis; Matzuk, Martin M.

doi:10.1371/journal.pbio.1000453

Cited by 231 publications

(188 citation statements)

References 86 publications

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“…Collectively, we conclude that paternal H3K4me1 catalyzed by the Mll3/4 complex is required for minor ZGA in the paternal genome, and its alteration causes developmental arrest in 4-to 8-cell stage embryos, which is distinct from major ZGA phenotype (i.e., arrest in 2-to 4-cell stages) induced by a-amanitin treatment, or depletion of Mll2 or Brg-1 [23,35]. Interestingly, this delayed growth retardation may be explained by a "stepwise" gene activation model; that is, one transcriptional wave triggers the following transcriptional waves during preimplantation development, and thus, ZGA transcripts and their protein products would be required for the progression of embryos beyond the 4-cell stage [36].…”

Section: Embo Reportsmentioning

confidence: 78%

“…Previously, Mll2 was reported to be required for early embryogenesis, based on the observations of decreased H3K4me2/3 in maternal PNs concomitant with~30% reduction of major ZGA and developmental arrest mainly at 2-cell stages, when it was knocked out [23]. To determine the enzyme responsible for H3K4 methylation during minor ZGA, we first investigated their expression levels from MII oocytes to 2-cell stage embryos using the Database of Transcriptome in Mouse Early Embryos (DBTMEE, http://dbtmee.…”

Section: Mll3/4 Expression In the Pn Stage Is Necessary For Early Prementioning

confidence: 99%

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Paternal H3K4 methylation is required for minor zygotic gene activation and early mouse embryonic development

et al. 2015

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Epigenetic modifications, such as DNA methylation and histone modifications, are dynamically altered predominantly in paternal pronuclei soon after fertilization. To identify which histone modifications are required for early embryonic development, we utilized histone K-M mutants, which prevent endogenous histone methylation at the mutated site. We prepared four single K-M mutants for histone H3.3, K4M, K9M, K27M, and K36M, and demonstrate that overexpression of H3.3 K4M in embryos before fertilization results in developmental arrest, whereas overexpression after fertilization does not affect the development. Furthermore, loss of H3K4 methylation decreases the level of minor zygotic gene activation (ZGA) predominantly in the paternal pronucleus, and we obtained similar results from knockdown of the H3K4 methyltransferase Mll3/4. We therefore conclude that H3K4 methylation, likely established by Mll3/4 at the early pronuclear stage, is essential for the onset of minor ZGA in the paternal pronucleus, which is necessary for subsequent preimplantation development in mice.

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Section: Embo Reportsmentioning

confidence: 78%

Section: Mll3/4 Expression In the Pn Stage Is Necessary For Early Prementioning

confidence: 99%

Paternal H3K4 methylation is required for minor zygotic gene activation and early mouse embryonic development

et al. 2015

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“…It has indeed been suggested that these Histone modifications, called bivalent marks, can poise developmental genes until later activation or repression, during differentiation (Bernstein et al, 2006). Interestingly, oocytes lacking MLL2 -a methyltransferase responsible of H3K4 tri-methylation during oocyte growth-display a failure in global transcriptional silencing which is in opposition to its believed role of active mark (Andreu-Vieyra et al, 2010).…”

Section: Three Dimensional Localization Of Constitutive Heterochromatmentioning

confidence: 99%

Genome organization and epigenetic marks in mouse germinal vesicle oocytes

Bonnet-Garnier¹,

Feuerstein²,

Chebrout³

et al. 2012

Int. J. Dev. Biol.

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During the final step of oogenesis, the oocyte nucleus is subject to large-scale modifications that correlate with transcriptional silencing. While oocytes with dense chromatin around the nucleolus are silent (SN, surrounded nucleolus), oocytes with uncondensed chromatin (NSN, non-surrounded nucleolus) are transcriptionally active. It is believed that epigenetic mechanisms that participate in gene expression regulation could play a role in this event. In this context, we examined the behaviour of heterochromatin and related histone modifications during the NSN to SN transition by immunostaining. Using fluorescent in situ hybridization on three dimensionalpreserved nuclei (3D-FISH), we also studied the distribution of centromeric, pericentromeric and ribosomal (rDNA) sequences in relation to the nucleolus (also called the nucleolus-like body, NLB). We observed that in NSN-type oocytes, pericentromeric heterochromatin is aggregated within chromocenters. In SN-type oocytes, pericentromeric heterochromatin and centromeres form a discontinuous ring around the NLB. rDNA sequences, which initially present a pearl necklace structure, gather together in seven highly condensed foci at the NLB periphery. H3K9me3 and H4K20me3 heterochromatin marks clearly label chromocenters, whereas H3K4me3 and H4K5ac are totally excluded from heterochromatin regions, even in the very compact SN-nuclei. Remarkably, H3K27me3 displays an intermediate behavior. It appears that GV oocyte nuclei exhibit a specific epigenetic landscape. Histone modifications, related to both active and repressive chromatin structures, seem to follow the large-scale chromatin movements that occur during the NSN to SN transition. We also demonstrate that, while heterochromatin regions re-localize around the NLB, rDNA sequences adopt a highly compact structure in SN-type oocytes.

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“…In addition to roles for histone methylation associated with repressive chromatin, trimethylation of H3K4, an active mark, has also been shown to be important in the female germline. Oocytespecific deletion of Mll2, an H3K4 methyltransferase, results in decreased levels of H3K4 methylation in peri-ovulatory oocytes and impairs either ovulation or pre-implantation development, depending on the timing of conditional deletion during oogenesis [63].…”

Section: Dna Methylationmentioning

confidence: 99%

Parental epigenetic control of embryogenesis: a balance between inheritance and reprogramming?

Gill

Erkek

Peters

2012

Current Opinion in Cell Biology

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At fertilization, fusion of two differentiated gametes forms the zygote that is capable of forming all of the varied cell lineages of an organism. It is widely thought that the acquisition of totipotency involves extensive epigenetic reprogramming of the germline state into an embryonic state. However, recent data argue that this reprogramming is incomplete and that substantial epigenetic information passes from one generation to the next. In this review we summarize the changes in chromatin states that take place during mammalian gametogenesis and examine the evidence that early mammalian embryogenesis may be affected by inheritance of epigenetic information from the parental generation.

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MLL2 Is Required in Oocytes for Bulk Histone 3 Lysine 4 Trimethylation and Transcriptional Silencing

Abstract: Conditional knockout mouse strategies identify the histone methyltranferase MLL2 as a key player in epigenetic reprogramming of female gametes.

Cited by 231 publications

References 86 publications

Paternal H3K4 methylation is required for minor zygotic gene activation and early mouse embryonic development

Paternal H3K4 methylation is required for minor zygotic gene activation and early mouse embryonic development

Genome organization and epigenetic marks in mouse germinal vesicle oocytes

Parental epigenetic control of embryogenesis: a balance between inheritance and reprogramming?

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