Narrow H3K4me2 is required for chicken PGC formation.


Zhang C(1), Zuo Q(1), Wang M(1), Chen H(2), He N(3)(4), Jin J(1), Li T(1), Jiang J(1), Yuan X(1), Li J(1), Shi X(1), Zhang M(1), Bai H(1), Zhang Y(1), Xu Q(1), Cui H(1), Chang G(1), Song J(5), Sun H(1), Zhang Y(1), Chen G(1), Li B(1).
Author information:
(1)Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, China.
(2)Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China.
(3)Department of Experimental Medical Science, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China.
(4)Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China.
(5)Department of Animal & Avian Sciences, University of Maryland, College Park, Maryland.


The development of primordial germ cells (PGCs) undergoes epigenetic modifications. The study of histone methylation in regulating PGCs is beneficial to understand the development and differentiation mechanism of germ stem cells. Notably, it provides a theoretical basis for directed induction and mass acquisition in vitro. However, little is known about the regulation of PGC formation by histone methylation. Here, we found the high enrichment of H3K4me2 in the blastoderm, genital ridges, and testis. Chromatin immunoprecipitation sequencing was performed and the results revealed that genomic H3K4me2 is dynamic in embryonic stem cells, PGCs, and spermatogonial stem cells. This trend was consistent with the H3K4me2 enrichment in the gene promoter region. Additionally, narrow region triggered PGC-related genes (Bmp4, Wnt5a, and Tcf7l2) and signaling pathways (Wnt and transforming growth factor-β). After knocking down histone methylase Mll2 in vitro and vivo, the level of H3K4me2 decreased, inhibiting Cvh and Blimp1 expression, then repressing the formation of PGCs. Taken together, our study revealed the whole genome map of H3K4me2 in the formation of PGCs, contributing to improve the epigenetic study in PGC formation and providing materials for bird gene editing and rescue of endangered birds.