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Hodges Lab

Human SMARCA5 is continuously required to maintain nucleosome spacing

AUTHORS

Bomber MLMonica L , Wang JJing , Liu QQi , Barnett KRKelly R , Layden HMHillary M , Hodges EEmily , Stengel KRKristy R , Hiebert SWScott W . Molecular cell. 2023 01 10; 83(4). 507-522.e6

ABSTRACT

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 G/S and during the S phase. SMARCA5 co-localized with CTCF and H2A.Z, and we found a rapid loss of CTCF DNA binding and disruption of nucleosomal phasing around CTCF binding sites. This spatiotemporal analysis indicates that SMARCA5 is continuously required for maintaining nucleosomal spacing.