Description:

The Simpson Querrey Institute for Epigenetics presents:

Nicola Iovino, PhD

Group Leader, Chromatin Regulation
Max Planck Institute, Freiburg, Germany

"Epigenetics of Early Development"

Fertilization occurs when the two gametes, after epigenetic reprogramming, fuse to produce a totipotent zygote. Although any defects in gametes’ reprogramming can cause infertility, the mechanisms underlying this process remain poorly understood.
My lab focuses on fundamental and translational aspects of chromatin biology in germ cells and early embryogenesis. We combine Drosophila genetics with mouse models to investigate three main lines of research: (i) germline inheritance of chromatin states, (ii) assembly and maturation of chromatin after fertilization (iii) 3D genome reorganization in early embryos. We showed that the H3K27me3 repressive histone mark is retained on post-meiotic oocytes. It is intergenerationally transmitted from the germline to the next generation showing for the first time that epigenetic information is also germline inherited and essential to regulate gene expression in the offspring. We could further show that de novo deposited histone variants and histone acetylation also regulate gene expression in the early embryo, revealing a completely unanticipated role for histone modification-mediated gene regulation at this developmental stage. In the early embryo, the nucleus is also organized de novo in a complex hierarchical folding pattern, including chromatin loops, topologically associating domains (TADs), and compartmental domains. We discovered a novel and fundamental role for HP1a in chromatin reorganization after fertilization. We showed that HP1a i) controls the general folding of chromosome arms, ii) controls the clustering and compaction of heterochromatic pericentromeric regions, and iii) contributes to the formation of the B compartment. In the long run, my lab will dissect the complete network that regulates chromatin remodelling in the early embryo in physiological and stressed conditions. Our investigations will reveal novel insights into the first steps in the formation of life and ultimately advance reproductive and regenerative medicine.

Selected references from my lab:
Zenk F., Zhan Y., et al. (2021) HP1 drives de novo 3D genome reorganization in early Drosophila embryos. Nature 593, 289–293
Ibarra-Morales D., et. Al. (2021) Histone variant H2AZ regulates zygotic genome activation.
Nature Communications 12, Article number: 7002 (2021)
Skvortsova K., et al (2018) Functions and mechanisms of epigenetic inheritance in animals. Nat Rev Mol Cell Biol.19(12):774-790
Zenk F., et al. (2017) Germ line–inherited H3K27me3 restricts enhancer function during maternal-to-zygotic transition. Science 6347, 212-216
Iovino N. (2014) Drosophila epigenome reorganization during oocyte differentiation and early embryogenesis. Brief Funct Genomics 13, 246-253.
Iovino N., et al. (2013) PRC2 controls Drosophila oocyte cell fate by repressing cell cycle genes. Dev Cell 26, 431-439.