Hoxc Gene Collinear Expression and Epigenetic Modifications Established during Embryogenesis Are Maintained until after Birth

Abstract

The Hox genes, which are organized into clusters on different chromosomes, are key regulators of embryonic anterior-posterior (A-P) body pattern formation and are expressed at specific times and in specific positions in developing vertebrate embryos. Previously, we have shown that histone methylation patterns are closely correlated with collinear Hox gene expression patterns along the A-P axis of E14.5 mouse embryos. Since histone modification is thought to play a crucial mechanistic role in the highly coordinated pattern of collinear Hox gene expression, we examined the maintenance of the spatial collinear expression pattern of Hoxc genes and the corresponding histone modifications during embryogenesis and in early postnatal mice. Hox expression patterns and histone modifications were analyzed by semi-quantitative RT-PCR and chromatin immunoprecipitation (ChIP)-PCR analyses, respectively. The spatiotemporal expression patterns of Hoxc genes in a cluster were maintained until the early postnatal stage (from E8.5 through P5). Examination of histone modifications in E14.5 and P5 tissues revealed that level of H3K27me3 is only a weak correlation with collinear Hoxc gene expression in the trunk regions although diminished in general, however the enrichment of H3K4me3 is strongly correlated with the gene expression in both stages. In summary, the initial spatiotemporal collinear expression pattern of Hoxc genes and epigenetic modifications are maintained after birth, likely contributing to the establishment of the gene expression code for position in the anatomic body axis throughout the entire life of the organism.

Transcriptional response ofHoxbgenes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis

“…As summarized in figure 6 , we found that genomic sequences flanking Hoxb4–6 genes, including RAREs controlling their expression in the neural tube, were clearly enriched for H3K27me3 marks in rostral NSPC cultures in comparison with caudal NSPCs, whereas H3K4me3 and H3K9/14ac marks showed opposite profiles. While lacking the power of high-throughput approaches, our results usefully complement previous data obtained with dissected explants from head and trunk regions of developing mice [ 57 , 59 , 61 , 62 ]. By taking advantage of culture conditions allowing symmetric NSPC self-renewal in vitro [ 40 ], our work provides comparison of nearly homogeneous populations of NSPCs, rather than tissue fragments where neural progenitors coexist with differentiated cells and non-neural cell types.…”

Genes Frequently Coexpressed with Hoxc8 Provide Insight into the Discovery of Target Genes

“…E14.5 embryos were dissected into three parts, brain, trunk anterior, and trunk posterior tissues, and then semi-quantitative RT-PCR was performed after isolating total RNA from each tissue. In agreement with previous reports ( Kwon et al, 2005 ; Min et al, 2012 ; 2013 ), Hoxc8 was strongly expressed in the trunk anterior and moderately expressed in the trunk posterior; it was not expressed in the brain ( Fig. 3 ).…”

CTCF‐mediated Chromatin Loop for the Posterior Hoxc Gene Expression in MEF Cells

“…Spatiotemporal collinear expression of Hox gene along the A–P axis in mouse embryos appears to be a consequence of epigenetic modifications of chromatin in which the 3' active domain (euchromatin) proceeds to posterior 5′ genes in the Hox cluster during development . Since separation of active and inactive domains in chromosomes is reported to be demarcated by the insulator binding protein CTCF in the chromatin barrier region , we next analyzed CTCF binding in the Hoxc cluster in both WT and Akt1 null MEFs.…”