Abstract

<h3>Summary</h3> <i>Hox</i> genes encode transcription factors that specify segmental identities along the Antero-Posterior body axis. These genes are organized in clusters, where their order corresponds to their activity along the body axis, an evolutionary conserved feature known as collinearity. In <i>Drosophila</i>, the BX-C cluster contains the three most posterior <i>Hox</i> genes, where their collinear activation incorporates progressive replacement of histone modifications, reorganization of 3D chromatin architecture and sequential activation of boundary elements and <i>cis</i>-regulatory regions. To dissect functional hierarchies, we compared chromatin organization in larvae and in cell lines, with a focus on the <i>Abd-B</i> gene. Our work establishes the importance of the Fab-7 boundary element for insulation between 3D domains marked by different histone modifications. Interestingly, we detected a non-canonical inversion of collinear chromatin dynamics at the <i>Abd-B</i> gene, with the active histone domain decreasing in size. This chromatin organization differentially instructed alternative <i>Abd-B</i> promoter use, thereby expanding the possibilities to regulate transcriptional output.

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