The histone H4 lysine 20 demethylase DPY-21 regulates the dynamics of condensin DC binding

组蛋白 H4 赖氨酸 20 去甲基化酶 DPY-21 调节凝缩蛋白 DC 结合的动力学

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作者:Laura Breimann, Ana Karina Morao, Jun Kim, David Sebastian Jimenez, Nina Maryn, Krishna Bikkasani, Michael J Carrozza, Sarah E Albritton, Maxwell Kramer, Lena Annika Street, Kustrim Cerimi, Vic-Fabienne Schumann, Ella Bahry, Stephan Preibisch, Andrew Woehler, Sevinç Ercan

Abstract

Condensin is a multi-subunit structural maintenance of chromosomes (SMC) complex that binds to and compacts chromosomes. Here, we addressed the regulation of condensin binding dynamics using Caenorhabditis 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 DPY-27 binding to X chromosomes. 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 sequencing data from the dpy-21 null mutant showed little change compared to wild-type data, uncoupling Hi-C-measured long-range DNA contacts from transcriptional repression of the X chromosomes. Taken 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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