SPT6 Regulates H3K14Ac Deposition in Mouse Embryonic Stem Cells [PRO-seq]

SPT6 (suppressor of Ty 6) is a conserved histone chaperone that facilitates transcription elongation, nucleosome reassembly, and RNA polymerase II progression. The functions of SPT6 in regulating chromatin remain not fully understood. Here we show that SPT6 localized to H3K14Ac enriched regions and promoted H3K14Ac densities in mouse embryonic stem cells (mESCs). Loss of SPT6 results in decreased H3K14Ac and transcription. Mechanistically, we showed that SPT6 enhances the chromatin binding levels of acetyltransferases KAT7 and KAT6A/KAT6B. In addition, we showed that SPT6 also promotes H3K14Ac in a KAT7/6A/6B independent manner. Our findings identify a vital role of SPT6 in maintaining the integrity of H3K14Ac profile in mESCs, thus suggesting a crosstalk between transcription machinery and H3K14Ac in mammals. Examination of nascent RNA in dTAG-SPT6 mESCs treated with DMSO or 100 nM dTAG-13 for 3h.