Skip to Main content Skip to Navigation
Journal articles

The chromatin remodelling protein LSH/HELLS regulates the amount and distribution of DNA hydroxymethylation in the genome

Abstract : Ten-Eleven Translocation (TET) proteins convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) leading to a dynamic epigenetic state of DNA that can influence transcription and chromatin organization. While TET proteins interact with complexes involved in transcriptional repression and activation, the overall understanding of the molecular mechanisms involved in TET-mediated regulation of gene expression still remains limited. Here, we show that TET proteins interact with the chromatin remodelling protein lymphoid-specific helicase (LSH/HELLS) in vivo and in vitro. In mouse embryonic fibroblasts (MEFs) and embryonic stem cells (ESCs) knock out of Lsh leads to a significant reduction of 5-hydroxymethylation amount in the DNA. Whole genome sequencing of 5hmC in wild-type versus Lsh knock-out MEFs and ESCs showed that in absence of Lsh, some regions of the genome gain 5hmC while others lose it, with mild correlation with gene expression changes. We further show that differentially hydroxymethylated regions did not completely overlap with differentially methylated regions indicating that changes in 5hmC distribution upon Lsh knock-out are not a direct consequence of 5mC decrease. Altogether, our results suggest that LSH, which interacts with TET proteins, contributes to the regulation of 5hmC levels and distribution in MEFs and ESCs.
Complete list of metadata

https://www.hal.inserm.fr/inserm-03357207
Contributor : Benoit Miotto Connect in order to contact the contributor
Submitted on : Tuesday, September 28, 2021 - 5:10:56 PM
Last modification on : Wednesday, November 24, 2021 - 9:54:21 AM

File

KEPI_A_1917152.pdf
Publication funded by an institution

Identifiers

Collections

Citation

Maud de Dieuleveult, Martin Bizet, Laurence Colin, Emilie Calonne, Martin Bachman, et al.. The chromatin remodelling protein LSH/HELLS regulates the amount and distribution of DNA hydroxymethylation in the genome. Epigenetics, Taylor & Francis, 2021, Online ahead of print. ⟨10.1080/15592294.2021.1917152⟩. ⟨inserm-03357207⟩

Share

Metrics

Record views

9

Files downloads

32