Lysine demethylase 7a regulates murine anterior-posterior development by modulating the transcription of Hox gene cluster

Yoshiki Higashijima, Nao Nagai, Masamichi Yamamoto, Taro Kitazawa, Yumiko K Kawamura, Akashi Taguchi, Natsuko Nakada, Masaomi Nangaku, Tetsushi Furukawa, Hiroyuki Aburatani, Hiroki Kurihara, Youichiro Wada, Yasuharu Kanki

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Abstract

Temporal and spatial colinear expression of the Hox genes determines the specification of positional identities during vertebrate development. Post-translational modifications of histones contribute to transcriptional regulation. Lysine demethylase 7A (Kdm7a) demethylates lysine 9 or 27 di-methylation of histone H3 (H3K9me2, H3K27me2) and participates in the transcriptional activation of developmental genes. However, the role of Kdm7a during mouse embryonic development remains to be elucidated. Herein, we show that Kdm7a-/- mouse exhibits an anterior homeotic transformation of the axial skeleton, including an increased number of presacral elements. Importantly, posterior Hox genes (caudally from Hox9) are specifically downregulated in the Kdm7a-/- embryo, which correlates with increased levels of H3K9me2, not H3K27me2. These observations suggest that Kdm7a controls the transcription of posterior Hox genes, likely via its demethylating activity, and thereby regulating the murine anterior-posterior development. Such epigenetic regulatory mechanisms may be harnessed for proper control of coordinate body patterning in vertebrates.

OriginalsprogEngelsk
Artikelnummer725
TidsskriftCommunications Biology
Vol/bind3
Nummer1
Sider (fra-til)725
ISSN2399-3642
DOI
StatusUdgivet - 30 nov. 2020
Udgivet eksterntJa

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