PT  - JOURNAL ARTICLE
AU  - Jayson J. Smith
AU  - Yutong Xiao
AU  - Nithin Parsan
AU  - Taylor N. Medwig-Kinney
AU  - Michael A. Q. Martinez
AU  - Frances E. Q. Moore
AU  - Nicholas J. Palmisano
AU  - Abraham Q. Kohrman
AU  - Mana Chandhok Delos Reyes
AU  - Rebecca C. Adikes
AU  - Simeiyun Liu
AU  - Sydney A. Bracht
AU  - Wan Zhang
AU  - Kailong Wen
AU  - Paschalis Kratsios
AU  - David Q. Matus
TI  - The SWI/SNF chromatin remodeling assemblies BAF and PBAF differentially regulate cell cycle exit and cellular invasion <em>in vivo</em>
AID  - 10.1101/2021.03.01.433447
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.01.433447
4099  - http://biorxiv.org/content/early/2021/09/01/2021.03.01.433447.short
4100  - http://biorxiv.org/content/early/2021/09/01/2021.03.01.433447.full
AB  - Chromatin remodelers such as the SWI/SNF complex coordinate metazoan development through broad regulation of chromatin accessibility and transcription, ensuring normal cell cycle control and cellular differentiation in a lineage-specific and temporally restricted manner. Mutations in genes encoding the structural subunits of chromatin, such as histone subunits, and chromatin regulating factors (CRFs) are associated with a variety of disease mechanisms including cancer metastasis, in which cancer co-opts cellular invasion programs functioning in healthy cells during development. Here we utilize Caenorhabditis elegans anchor cell (AC) invasion as an in vivo model to identify the suite of chromatin agents and CRFs that promote cellular invasiveness. We demonstrate that the SWI/SNF ATP-dependent chromatin remodeling complex is a critical regulator of AC invasion, with pleiotropic effects on both G0 cell cycle arrest and activation of invasive machinery. Using targeted protein degradation and enhanced RNA interference (RNAi) vectors, we show that SWI/SNF contributes to AC invasion in a dose-dependent fashion, with lower levels of activity in the AC corresponding to aberrant cell cycle entry and increased loss of invasion. Our data specifically implicate the SWI/SNF BAF assembly in the regulation of the G0 cell cycle arrest in the AC, whereas the SWI/SNF PBAF assembly promotes AC invasion via cell cycle-independent mechanisms, including attachment to the basement membrane (BM) and activation of the pro-invasive fos-1/FOS gene. Together these findings demonstrate that the SWI/SNF complex is necessary for two essential components of AC invasion: arresting cell cycle progression and remodeling the BM. The work here provides valuable single-cell mechanistic insight into how the SWI/SNF assemblies differentially contribute to cellular invasion and how SWI/SNF subunit-specific disruptions may contribute to tumorigeneses and cancer metastasis.SUMMARY STATEMENT Cellular invasion through the basement membrane by the C. elegans anchor cell requires both BAF and PBAF SWI/SNF assemblies to arrest the cell cycle and promote the expression of pro-invasive genes.Competing Interest StatementThe authors have declared no competing interest.