An ATPase-deficient variant of the SNF2 family member HELLS shows altered dynamics at pericentromeric Heterochromatin

Lungu, Cristiana, Muegge, Kathrin, Jeltsch, Albert and Jurkowska, Renata Z. ORCID: https://orcid.org/0000-0002-4507-2222 2015. An ATPase-deficient variant of the SNF2 family member HELLS shows altered dynamics at pericentromeric Heterochromatin. Journal of Molecular Biology 427 (10) , pp. 1903-1915. 10.1016/j.jmb.2015.03.014

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Abstract

The HELLS (helicase, lymphoid specific, also known as lymphoid-specific helicase) protein is related to the SNF2 (sucrose non-fermentable 2) family of chromatin remodeling ATPases. It is required for efficient DNA methylation in mammals, particularly at heterochromatin-located repetitive sequences. In this study, we investigated the interaction of HELLS with chromatin and used an ATPase-deficient HELLS variant to address the role of ATP hydrolysis in this process. Chromatin fractionation experiments demonstrated that, in the absence of the ATPase activity, HELLS is retained at the nuclear matrix compartment, defined in part by lamin B1. Microscopy studies revealed a stronger association of the ATPase-deficient mutant with heterochromatin. These results were further supported by fluorescence recovery after photobleaching measurements, which showed that, at heterochromatic sites, wild-type HELLS is very dynamic, with a recovery half-time of 0.8 s and a mobile protein fraction of 61%. In contrast, the ATPase-deficient mutant displayed 4.5-s recovery half-time and a reduction in the mobile fraction to 30%. We also present evidence suggesting that, in addition to the ATPase activity, a functional H3K9me3 signaling pathway contributes to an efficient release of HELLS from pericentromeric chromatin. Overall, our results show that a functional ATPase activity is not required for the recruitment of HELLS to heterochromatin, but it is important for the release of the enzyme from these sites.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Elsevier
ISSN:	0022-2836
Date of First Compliant Deposit:	31 October 2019
Date of Acceptance:	20 March 2015
Last Modified:	26 Oct 2022 08:02
URI:	https://orca.cardiff.ac.uk/id/eprint/126451

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