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Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation.

Ancelin K, Syx L, Borensztein M, Ranisavljevic N, Vassilev I, Briseño-Roa L, Liu T, Metzger E, Servant N, Barillot E, Chen CJ, Schüle R, Heard E - Elife (2016)

Bottom Line: Upon fertilization, the highly specialised sperm and oocyte genomes are remodelled to confer totipotency.The mechanisms of the dramatic reprogramming events that occur have remained unknown, and presumed roles of histone modifying enzymes are just starting to be elucidated.At the transcriptional level, the switch of the maternal-to-zygotic transition fails to be induced properly and LINE-1 retrotransposons are not properly silenced.

View Article: PubMed Central - PubMed

Affiliation: Institut Curie, Paris, France.

ABSTRACT
Upon fertilization, the highly specialised sperm and oocyte genomes are remodelled to confer totipotency. The mechanisms of the dramatic reprogramming events that occur have remained unknown, and presumed roles of histone modifying enzymes are just starting to be elucidated. Here, we explore the function of the oocyte-inherited pool of a histone H3K4 and K9 demethylase, LSD1/KDM1A during early mouse development. KDM1A deficiency results in developmental arrest by the two-cell stage, accompanied by dramatic and stepwise alterations in H3K9 and H3K4 methylation patterns. At the transcriptional level, the switch of the maternal-to-zygotic transition fails to be induced properly and LINE-1 retrotransposons are not properly silenced. We propose that KDM1A plays critical roles in establishing the correct epigenetic landscape of the zygote upon fertilization, in preserving genome integrity and in initiating new patterns of genome expression that drive early mouse development.

No MeSH data available.


Related in: MedlinePlus

DOI:http://dx.doi.org/10.7554/eLife.08851.019
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fig7: DOI:http://dx.doi.org/10.7554/eLife.08851.019

Mentions: In order to show the raw data of fluorescence measurements, we provide a figure (Author response image 2) in which are presented the distributions of the integrated intensities measured per nucleus for each of the embryos (control or mutant) stained with anti-H3K4me3, anti-H3K9me3 or anti-H3K27me3. These raw data were used to produce the ratio of changes between control and mutant embryos plotted in Figure 3 or Figure 3—figure supplement 1, under each image panel.


Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation.

Ancelin K, Syx L, Borensztein M, Ranisavljevic N, Vassilev I, Briseño-Roa L, Liu T, Metzger E, Servant N, Barillot E, Chen CJ, Schüle R, Heard E - Elife (2016)

DOI:http://dx.doi.org/10.7554/eLife.08851.019
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4829419&req=5

fig7: DOI:http://dx.doi.org/10.7554/eLife.08851.019
Mentions: In order to show the raw data of fluorescence measurements, we provide a figure (Author response image 2) in which are presented the distributions of the integrated intensities measured per nucleus for each of the embryos (control or mutant) stained with anti-H3K4me3, anti-H3K9me3 or anti-H3K27me3. These raw data were used to produce the ratio of changes between control and mutant embryos plotted in Figure 3 or Figure 3—figure supplement 1, under each image panel.

Bottom Line: Upon fertilization, the highly specialised sperm and oocyte genomes are remodelled to confer totipotency.The mechanisms of the dramatic reprogramming events that occur have remained unknown, and presumed roles of histone modifying enzymes are just starting to be elucidated.At the transcriptional level, the switch of the maternal-to-zygotic transition fails to be induced properly and LINE-1 retrotransposons are not properly silenced.

View Article: PubMed Central - PubMed

Affiliation: Institut Curie, Paris, France.

ABSTRACT
Upon fertilization, the highly specialised sperm and oocyte genomes are remodelled to confer totipotency. The mechanisms of the dramatic reprogramming events that occur have remained unknown, and presumed roles of histone modifying enzymes are just starting to be elucidated. Here, we explore the function of the oocyte-inherited pool of a histone H3K4 and K9 demethylase, LSD1/KDM1A during early mouse development. KDM1A deficiency results in developmental arrest by the two-cell stage, accompanied by dramatic and stepwise alterations in H3K9 and H3K4 methylation patterns. At the transcriptional level, the switch of the maternal-to-zygotic transition fails to be induced properly and LINE-1 retrotransposons are not properly silenced. We propose that KDM1A plays critical roles in establishing the correct epigenetic landscape of the zygote upon fertilization, in preserving genome integrity and in initiating new patterns of genome expression that drive early mouse development.

No MeSH data available.


Related in: MedlinePlus