A noncatalytic activity of the H4K20 demethylase DPY-21 regulates condensin DC binding

Breimann, L.; Morao, A. K.; Kim, J.; Jimenez, D.; Maryn, N.; Bikkasani, K.; Carrozza, M. J.; Albritton, S. E.; Kramer, M.; Street, L. A.; Cerimi, K.; Schumann, V.-F.; Bahry, E.; Preibisch, S.; Woehler, A.; Ercan, S.

doi:10.1101/2021.04.11.438056

bioRxiv · 10.1101/2021.04.11.438056

A noncatalytic activity of the H4K20 demethylase DPY-21 regulates condensin DC binding

Breimann, L.·Morao, A. K.·Kim, J.·Jimenez, D.·Maryn, N.·Bikkasani, K.·Carrozza, M. J.·Albritton, S. E.·Kramer, M.·Street, L. A.·Cerimi, K.·Schumann, V.-F.·Bahry, E.·Preibisch, S.·Woehler, A.·Ercan, S.

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Abstract

Condensin is a multi-subunit SMC complex that binds to and compacts chromosomes. Here we addressed the regulation of condensin binding dynamics using C. elegans condensin DC, which represses X chromosomes in hermaphrodites for dosage compensation. We established fluorescence recovery after photobleaching (FRAP) using the SMC4 homolog DPY-27 and showed that a well-characterized ATPase mutation abolishes its binding. Next, we performed FRAP in the background of several chromatin modifier mutants that cause varying degrees of X-chromosome derepression. The greatest effect was in a null mutant of the H4K20me2 demethylase DPY-21, where the mobile fraction of condensin DC reduced from [~]30% to 10%. In contrast, a catalytic mutant of dpy-21 did not regulate condensin DC mobility. Hi-C data in the dpy-21 null mutant showed little change compared to wild type, uncoupling Hi-C measured long-range DNA contacts from transcriptional repression of the X chromosomes. Together, our results indicate that DPY-21 has a non-catalytic role in regulating the dynamics of condensin DC binding, which is important for transcription repression.

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Breimann, L., Morao, A. K., Kim, J., Jimenez, D., Maryn, N., Bikkasani, K., Carrozza, M. J., Albritton, S. E., Kramer, M., Street, L. A., Cerimi, K., Schumann, V.-F., Bahry, E., Preibisch, S., Woehler, A., Ercan, S.. 2021-04-12. A noncatalytic activity of the H4K20 demethylase DPY-21 regulates condensin DC binding. https://doi.org/10.1101/2021.04.11.438056

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