Short description of the group/project/topic of research
Sex-chromosome dosage compensation is one of the most fascinating problems in biology. Females carry two X chromosomes, while males only have one. Despite this imbalance, males and females express X-linked genes at roughly equal levels. How is the correct dosage of X-linked genes achieved? In flies, the histone acetyltransferase MOF associates with the MSL complex to specifically hyperacetylate histone H4 at lysine 16 throughout the male X chromosome, thereby triggering transcriptional upregulation and achieving dosage compensation of X-linked genes. Our latest research revealed that the long non-coding RNA component roX2 helps the MSL complex to achieve its exquisite specificity for the male X chromosome by forming a stable phase-separated hydrogel with protein component MSL2 (Keller Valsecchi et al., 2021 Nature). In a separate study we found that the maternal deposition of H4K16ac provides oocytes with instructive information which is indispensable for the onset of dosage compensation during embryonic development. Loss of maternal MOF leads to compromised nucleosome accessibility, 3D genome organization and transcription and leads to lethality in the male offspring (Samata et al., 2020 Cell).
We have also recently discovered that the mammalian MSL2 homologue regulates dosage of haploinsufficient genes in mice (Sun et al., 2023 Nature). We are therefore interested to explore the conservation of this phenomenon and mechanism in flies.
The recruited postdoc will work on advancing our mechanistic understanding of the dosage compensation mechanism, including factors driving its initiation and maintenance using genomic, biochemical and super-resolution imaging approaches.
Qualifications:
- Applicants should have a PhD in molecular biology, biochemistry, genetics, imaging, bioinformatics or a related discipline
- Several years of experience working with Drosophila melanogaster is required
- Candidates should have a strong publication record
- The ability to work effectively in a team, possess good communication skills and have prior experience in the supervision of graduate students would be favourable
Additional information
Recent project-relevant publications:
Sun Y, Wiese M, Hmadi R, … Akhtar A. (2023) MSL2 ensures biallelic gene expression in mammals. Nature 624:173-181.
Keller Valsecchi CI, Basilicata MF, ... Akhtar A. (2021) RNA nucleation by MSL2 induces selective X chromosome compartmentalization. Nature 589:137-142.
Samata M, Alexiadis A, ... Akhtar A. (2020) Intergenerationally maintained histone H4 lysine 16 acetylation is instructive for future gene activation. Cell 182:127-144.
Link to PI’s webpage
https://www.ie-freiburg.mpg.de/akhtar