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

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.DOI: http://dx.doi.org/10.7554/eLife.08851.001

Ssm1b expression and function in germ cells of adult mice and in early embryos

“…Yet, transcription is generally silent during this period of development (Hamatani, Carter, Sharov, & Ko, ), instead relying on translation of maternally stored Ssm1b transcript to suppress repetitive elements. This phenomenon highlights the importance of maternal gene expression, which was also previously observed for long interspersed transposable elements (e.g., LINE‐1), for which maternally inherited KDM1A is required to suppress their activity during preimplantation development (Ancelin et al, ).…”

Hypertranscription in Development, Stem Cells, and Regeneration

“…Maternally-deleted Brg1 embryos exhibit a reduction in total nascent transcription and decreased expression of a subset of RNA Pol II-driven ZGA transcripts (Bultman, 2006). Maternal Lsd1/Kdm1a, a histone demethylase, may also play an important role in ZGA, as mutant embryos tend to arrest at the 2-cell stage with impaired upregulation of ZGA-associated transcripts (Ancelin et al, 2016). It remains unclear what specific chromatin features these factors induce in the genome of the early embryo and how their action is coordinated during ZGA.…”

Targeted treatment for glioblastoma: Revisiting conventional strategies and novel targets

“…KDM1A, temel olarak H3K4 ve H3K9 üzerinde bulunan metil gruplarını ayıra-rak, embriyonik süreçte görülen epigenetik yeniden programlamada görev alır (50,51) . Sareddy ve ark.…”