Abstract
In Drosophila melanogaster the single male chromosome X undergoes an average twofold transcriptional upregulation for balancing the transcriptional output between sexes. Previous literature hypothesised that a global change in chromosome structure may accompany this process. However, recent studies based on Hi-C failed to detect these differences. Here we show that global conformational differences are specifically present in the male chromosome X and detectable using Hi-C data on sex-sorted embryos, as well as male and female cell lines, by leveraging custom data analysis solutions. We find the male chromosome X has more mid-/long-range interactions. We also identify differences at structural domain boundaries containing BEAF-32 in conjunction with CP190 or Chromator. Weakening of these domain boundaries in male chromosome X co-localizes with the binding of the dosage compensation complex and its co-factor CLAMP, reported to enhance chromatin accessibility. Together, our data strongly indicate that chromosome X dosage compensation affects global chromosome structure.
Highlights
In Drosophila melanogaster the single male chromosome X undergoes an average twofold transcriptional upregulation for balancing the transcriptional output between sexes
When considering the log[2] ratio between the independently normalized Hi-C data for chromosome X (chrX), we noticed a relative increase in the male over female Hi-C signal ratio at mid-/long-range distances (500 kb–1 Mb), with many points in the contact matrix showing a signal of relatively higher magnitude in the male chrX (Fig. 1a)
We checked the overlap with the previous classification (Same, Appearing, Disappearing classes) and we found that the BEAF-32 peak (BEAF) + and CP190 or Chromator peak (CP/CH) + boundaries are mostly overlapping with boundaries which were classified as Same or Disappearing on chrX (Fig. 4d)
Summary
In Drosophila melanogaster the single male chromosome X undergoes an average twofold transcriptional upregulation for balancing the transcriptional output between sexes. We identify differences at structural domain boundaries containing BEAF-32 in conjunction with CP190 or Chromator Weakening of these domain boundaries in male chromosome X co-localizes with the binding of the dosage compensation complex and its co-factor CLAMP, reported to enhance chromatin accessibility. In Drosophila melanogaster, DC is achieved by the twofold upregulation of active genes on the single copy chromosome X (chrX) in males. Whereas Schauer et al.[9] showed that, after binding, the DCC spreads in cis along chrX from the initial binding sites to all of the active genes, aided by the 3D chromatin conformation around PionX sites. Hi-C opened the possibility to characterize physical proximity of any pair of genomic loci This allowed the identification of higher order genome compartments distinguished by active or inactive chromatin[12]. If any, are observed locally in chromatin interactions[22]
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