@article{bfe14ae82f5a434b8433d7edef711770,
title = "Human SMARCA5 is continuously required to maintain nucleosome spacing",
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 G1/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.",
keywords = "ATAC-seq, CTCF, H2A.Z, MNase-seq, PRO-seq, SMARCA5, chromatin, nucleosome repeat length",
author = "Bomber, {Monica L.} and Jing Wang and Qi Liu and Barnett, {Kelly R.} and Layden, {Hillary M.} and Emily Hodges and Stengel, {Kristy R.} and Hiebert, {Scott W.}",
note = "Funding Information: We especially thank Dr. Michael Stadler (Friedrich Miescher Institute for Biomedical Research and the Swiss Institute of Bioinformatics, Basel, Switzerland) for sharing code and for helpful guidance in using this code to calculate NRL. We also thank the members of the Hiebert lab for helpful discussions, reagents, and advice. We thank the Flow Cytometry, Chemical Synthesis, and Genome Sciences Shared Resources for their services and support. Core services were performed through the Vanderbilt Digestive Disease Research grant (NIDDK P30DK58404) and the Vanderbilt-Ingram Cancer Center support grant (NCI P30CA68485). This work was supported by the T.J. Martell Foundation, the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation, National Institutes of Health grants (RO1-CA164605, R01-CA255446-01A1, and T32-CA009582-33), and a Department of Defense grant (W81XWH-20-1-0522). The project described was also supported by the National Center for Research Resources, grant UL1 RR024975-01 and is now at the National Center for Advancing Translational Sciences, Grant 2 UL1 TR000445-06. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Conceptualization, M.L.B. and S.W.H.; methodology, M.L.B. K.R.B. and K.R.S.; investigation, K.R.B. M.L.B. and K.R.S.; formal analysis, M.L.B. J.W. Q.L. K.R.B. and K.R.S.; writing –original draft, M.L.B. K.R.S. and S.W.H.; writing – review & editing, K.R.S. M.L.B. E.H. J.W. Q.L. K.R.B. H.M.L. and S.W.H.; visualization, M.L.B. K.R.S. and S.W.H.; supervision, E.H. K.R.S. and S.W.H.; funding acquisition, S.W.H. K.R.S. and E.H. Although S.W.H. received research funding from Incyte Inc. through the Vanderbilt-Incyte Alliance, these funds did not support this work. S.W.H. is also a scientific advisor for the Edward P. Evans Foundation. We support inclusive, diverse, and equitable conduct of research. One or more of the authors of this paper self-identifies as a gender minority in their field of research. One or more of the authors of this paper self-identifies as a member of the LGBTQIA+ community. One or more of the authors of this paper self-identifies as living with a disability. Funding Information: We especially thank Dr. Michael Stadler (Friedrich Miescher Institute for Biomedical Research and the Swiss Institute of Bioinformatics, Basel, Switzerland) for sharing code and for helpful guidance in using this code to calculate NRL. We also thank the members of the Hiebert lab for helpful discussions, reagents, and advice. We thank the Flow Cytometry, Chemical Synthesis, and Genome Sciences Shared Resources for their services and support. Core services were performed through the Vanderbilt Digestive Disease Research grant ( NIDDK P30DK58404 ) and the Vanderbilt-Ingram Cancer Center support grant ( NCI P30CA68485 ). This work was supported by the T.J. Martell Foundation , the Robert J. Kleberg , Jr. and Helen C. Kleberg Foundation , National Institutes of Health grants ( RO1-CA164605 , R01-CA255446-01A1 , and T32-CA009582-33 ), and a Department of Defense grant ( W81XWH-20-1-0522 ). The project described was also supported by the National Center for Research Resources , grant UL1 RR024975-01 and is now at the National Center for Advancing Translational Sciences , Grant 2 UL1 TR000445-06 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Funding Information: Although S.W.H. received research funding from Incyte Inc. through the Vanderbilt-Incyte Alliance, these funds did not support this work. S.W.H. is also a scientific advisor for the Edward P. Evans Foundation. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2023",
month = feb,
day = "16",
doi = "10.1016/j.molcel.2022.12.018",
language = "English (US)",
volume = "83",
pages = "507--522.e6",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "4",
}