Biology subjects

Ancelin, K.

Publications and source records attributed to Ancelin, K..

3 recordsLinked to original sources

bioRxiv2026

The human X chromosome in sexual differentiation and reproduction: is the X still sexy?

The human X chromosome (chrX) has long been proposed to be enriched in genes involved in brain development, reproduction and sexual differentiation, earning the epithet of "smart and sexy" chromosome. Many studies have confirmed that the chrX is indeed "smart", but it is less clear whether "sexy" still holds true. Here, we investigated human X-linked genes with respect to their expression levels across tissues and cell types, their annotated functions, and their association with monogenic disorders affecting sexual differentiation and reproduction (SDR). We confirm that many brain and sex-specific tissues show high X-to-autosome (X:A) expression ratios; however, paradoxically, some of the corresponding main cell types, such as neurons or prostatic or endometrial cells, show X:A ratios below the average. In contrast, cell types such as blood and vascular cells have elevated X:A ratios, suggesting that they contribute to the high ratios observed at the tissue bulk level. Analysing the most highly expressed genes across tissues and cell types, we observed a significant enrichment in chrX genes for testes, spermatogonia and Sertoli cells. Interestingly, monogenic disorders with SDR phenotypes showed a significant enrichment of chrX genes only when related to male-specific conditions. Our study thus supports a male-biased view of the "sexy" human chrX, whereby it is particularly enriched in genes highly expressed in testicular cell types and in genes involved in male reproductive monogenic disorders. Intriguingly, these genes overlap very little, suggesting an important disconnect between expression levels and clinical associations, at least on the X chromosome.

genomics↗

bioRxiv2022

Inversion of a topological domain leads to restricted changes in its gene expression and affects inter-domain communication

The interplay between the topological organization of the genome and the regulation of gene expression remains unclear. Depletion of molecular factors underlying genome topology, such as CTCF and cohesin, leads to modest alterations in gene expression, while genomic rearrangements involving boundaries of topologically associating domains (TADs) disrupt normal gene expression and can lead to pathological phenotypes. Here we inverted an almost entire TAD (245kb out of 300kb) within the X-inactivation centre (Xic), leaving its boundaries intact. This led to a significant rearrangement of topological contacts within the TAD, mostly in accordance to the orientation of underlying CTCF binding sites but suggesting heterogeneity in the "contact" potential of different CTCF sites. The inversion also led to increased contact insulation with the neighbouring TAD. Expression of most genes within the inverted TAD remained unaffected in mouse embryonic stem cells and during differentiation. Interestingly, expression in the neighbouring TAD of the noncoding transcript Xist, which controls X-chromosome inactivation, was ectopically upregulated. The same inversion in mouse embryos led to a bias in Xist expression, but X-inactivation choice ratios did not significantly deviate from wild type. Smaller deletions and inversions of specific clusters of CTCF sites within the TAD led to similar results: rearrangement of contacts, limited changes in local gene expression but significant changes in Xist expression. Our study suggests that the wiring of regulatory interactions within a TAD can influence the expression of genes in neighbouring TADs, highlighting the existence of mechanisms for inter-TAD communication.

genomics↗

bioRxiv2017

Differential epigenetic landscapes and transcription factors explain X-linked gene behaviours during X-chromosome reactivation in the mouse inner cell mass

X-chromosome inactivation (XCI) is established in two waves during mouse development. First, silencing of the paternal X chromosome (Xp) is triggered, with transcriptional repression of most genes and enrichment of epigenetic marks such as H3K27me3 being achieved in all cells by the early blastocyst stage. XCI is then reversed in the inner cell mass (ICM), followed by a second wave of maternal or paternal XCI, in the embryo-proper. Although the role of Xist RNA in triggering XCI is now clear, the mechanisms underlying Xp reactivation in the inner cell mass have remained enigmatic. Here we use in vivo single cell approaches (allele-specific RNAseq, nascent RNA FISH and immunofluorescence) and find that different genes show very different timing of reactivation. We observe that the genes reactivate at different stages and that initial enrichment in H3K27me3 anti-correlates with the speed of reactivation. To define whether this repressive histone mark is lost actively or passively, we investigate embryos mutant for the X-encoded H3K27me3 demethylase, UTX. Xp genes that normally reactivate slowly are retarded in their reactivation in Utx mutants, while those that reactive rapidly are unaffected. Therefore, efficient reprogramming of some X-linked genes in the inner cell mass is very rapid, indicating minimal epigenetic memory and potentially driven by transcription factors, whereas others may require active erasure of chromatin marks such as H3K27me3.

developmental biology↗