biostudies-literatureBomber MLNCATS NIH HHSNCRR NIH HHSNIDDK NIH HHSNCI NIH HHSNIGMS NIH HHS507-522.e6https://www.ebi.ac.uk/biostudies/studies/S-EPMC9974918biostudies-literatureUnknown83(4)Genetic models suggested that SMARCA5 was required for DNA-templated events including transcription, DNA replication, and DNA repair. We engineered a degron tag into the endogenous alleles of SMARCA5, a catalytic component of the imitation switch complexes in three different human cell lines to define the effects of rapid degradation of this key regulator. Degradation of SMARCA5 was associated with a rapid increase in global nucleosome repeat length, which may allow greater chromatin compaction. However, there were few changes in nascent transcription within the first 6 h of degradation. Nevertheless, we demonstrated a requirement for SMARCA5 to control nucleosome repeat length at G₁/S and during the S phase. SMARCA5 co-localized with CTCF and H2A.Z, and we found a rapid loss ofMolecular cellHuman SMARCA5 is continuously required to maintain nucleosome spacing.PMC9974918R01 CA164605R01 CA255446F32 CA174162R35 GM147213UL1 RR024975P30 CA068485P30 DK058404T32 CA009582UL1 TR000445Hodges ELayden HMLiu QStengel KRBomber MLHiebert SWWang JBarnett KRfalseHuman SMARCA5 is continuously required to maintain nucleosome spacing.Genetic models suggested that SMARCA5 was required for DNA-templated events including transcription, DNA replication, and DNA repair. We engineered a degron tag into the endogenous alleles of SMARCA5, a catalytic component of the imitation switch complexes in three different human cell lines to define the effects of rapid degradation of this key regulator. Degradation of SMARCA5 was associated with a rapid increase in global nucleosome repeat length, which may allow greater chromatin compaction. However, there were few changes in nascent transcription within the first 6 h of degradation. Nevertheless, we demonstrated a requirement for SMARCA5 to control nucleosome repeat length at G₁/S and during the S phase. SMARCA5 co-localized with CTCF and H2A.Z, and we found a rapid loss of2023-01-01T00:00:00Z2023 Feb2026-05-28T21:55:07.404Z2025-02-18T23:23:54.464ZS-EPMC99749183663095410.1016/j.molcel.2022.12.018