H4K16ac activates retrotransposons and contributes to their cis regulatory function [ATAC-seq]

Mammalian genomes harbour a large number of transposable elements (TEs) and their remnants. Most TEs are incapable of retrotransposition, however, they have evolved as cis-regulatory elements (CREs), enabling them to recruit host-encoded factors. Understanding the contribution of TEs in the regulation of the mammalian genome is an active area of research. Here we show that the male-specific lethal (MSL) complex-mediated acetylation of histone H4 lysine 16 (H4K16ac) regulates the transcription of TEs. Furthermore, H4K16ac marked TEs function as a rich source of cis regulatory elements in the human genome, wherein H4K16ac acts by maintaining the permissive chromatin structure and promoting the transcription of these TEs. ATAC-Seq was performed for H9 hPSCs stable cell lines expressing non-targeting shRNA (control/Scr.) and MSL3 knockdown (MSL3 KD, two independent shRNAs). Each sample was processed in three biological replicates. For TDFs, wild type (icas9) iCAS9 line and MSL3 knockout (MSL3 KO) line were used. Each sample was processed in two biological replicates.