RT Journal Article
SR Electronic
T1 H4K16ac activates the transcription of transposable elements and contributes to their cis-regulatory function
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.04.29.488986
DO 10.1101/2022.04.29.488986
A1 Debosree Pal
A1 Manthan Patel
A1 Fanny Boulet
A1 Jayakumar Sundarraj
A1 Olivia A Grant
A1 Miguel R. Branco
A1 Srinjan Basu
A1 Silvia Santos
A1 Nicolae Radu Zabet
A1 Paola Scaffidi
A1 Madapura M Pradeepa
YR 2022
UL http://biorxiv.org/content/early/2022/11/16/2022.04.29.488986.abstract
AB Mammalian genomes harbour a large number of transposable elements (TEs) and their remnants. Many epigenetic repression mechanisms are known to silence TE transcription. However, TEs are upregulated during early development, neuronal lineage, and cancers, although the epigenetic factors contributing to the transcription of TEs have yet to be fully elucidated. Here we demonstrated that the male-specific lethal (MSL) complex mediated acetylation of histone H4 lysine 16 (H4K16ac) activates transcription of long interspersed nuclear elements (LINE1, L1) and long terminal repeats (LTRs). Furthermore, we show that the H4K16ac marked L1 and LTR subfamilies function as enhancers and are enriched with chromatin features associated with active enhancers and looping factors. L1 and LTRs enriched with histone acetylations are bound by chromatin looping factors and these regions loop with genes. CRISPR-based epigenetic perturbation and genetic deletion of L1s reveal that H4K16ac marked L1s and LTRs regulate the expression of genes in cis. Overall, TEs enriched with H4K16ac contribute to the cis-regulatory landscape of a significant portion of the mammalian genome by maintaining an active chromatin landscape at TEs.One Sentence Summary H4K16ac activates LINE1 and ERV/LTR transcription and rewires the cis-regulatory landscape of a significant portion of the mammalian genome by increasing the transcriptional activity at TEs.Competing Interest StatementThe authors have declared no competing interest.