Lysine demethylase 7a regulates the anterior-posterior development in mouse by modulating the transcription ofHoxgene cluster

SUMMARYTemporal and spatial colinear expression of theHoxgenes 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 di-methylation of histone H3 (H3K9me2) and participates in the transcriptional activation of developmental genes. However, the role of Kdm7a during mouse embryonic development remains to be elucidated. Here, we show thatKdm7a−/−mouse exhibits an anterior homeotic transformation of the axial skeleton, including an increased number of presacral elements. Importantly, posteriorHoxgenes (caudally fromHox9) are specifically downregulated in theKdm7a−/−embryo, which correlates with increased levels of H3K9me2. These observations suggest that Kdm7a controls the transcription of posteriorHoxgenes, likely via its demethylating activity, and thereby regulating the murine anterior-posterior development. Such epigenetic regulatory mechanisms may be harnessed for the proper control of coordinate body patterning in vertebrates.