@article{682b7d262f824a3ba81261e6f91d593d,
title = "p53 mediates target gene association with nuclear speckles for amplified RNA expression",
abstract = "Nuclear speckles are prominent nuclear bodies that contain proteins and RNA involved in gene expression. Although links between nuclear speckles and gene activation are emerging, the mechanisms regulating association of genes with speckles are unclear. We find that speckle association of p53 target genes is driven by the p53 transcription factor. Focusing on p21, a key p53 target, we demonstrate that speckle association boosts expression by elevating nascent RNA amounts. p53-regulated speckle association did not depend on p53 transactivation functions but required an intact proline-rich domain and direct DNA binding, providing mechanisms within p53 for regulating gene-speckle association. Beyond p21, a substantial subset of p53 targets have p53-regulated speckle association. Strikingly, speckle-associating p53 targets are more robustly activated and occupy a distinct niche of p53 biology compared with non-speckle-associating p53 targets. Together, our findings illuminate regulated speckle association as a mechanism used by a transcription factor to boost gene expression.",
keywords = "chromosome architecture, gene activation, nuclear positioning, nuclear speckles, p21, p53, phase-separated nuclear bodies, transcription, transcription factor",
author = "Alexander, {Katherine A.} and Allison Cot{\'e} and Nguyen, {Son C.} and Liguo Zhang and Omid Gholamalamdari and Paula Agudelo-Garcia and Enrique Lin-Shiao and Tanim, {K. M.A.} and Joan Lim and Nicolas Biddle and Dunagin, {Margaret C.} and Good, {Charly R.} and Mendoza, {Mariel R.} and Little, {Shawn C.} and Andrew Belmont and Joyce, {Eric F.} and Arjun Raj and Berger, {Shelley L.}",
note = "Funding Information: S.L.B. acknowledges support from NIH grant R01CA078831 . K.A.A. acknowledges support from NIH grant F32CA221010 . A.R. acknowledges support from NIH grant U01DK127405 , NIH grant 4DN U01 HL129998 , and the NIH Center for Photogenomics . A.B. acknowledges health grants R01 GM58460 and U54 DK107965 . E.F.J. acknowledges support from NIH /National Institute of General Medical Sciences (NIGMS) grant R35GM128903. Funding Information: S.L.B. acknowledges support from NIH grant R01CA078831. K.A.A. acknowledges support from NIH grant F32CA221010. A.R. acknowledges support from NIH grant U01DK127405, NIH grant 4DN U01 HL129998, and the NIH Center for Photogenomics. A.B. acknowledges health grants R01 GM58460 and U54 DK107965. E.F.J. acknowledges support from NIH/National Institute of General Medical Sciences (NIGMS) grant R35GM128903. Conceptualization, K.A.A. and S.L.B.; Methodology, K.A.A. E.L.-S. K.M.A.T. and S.L.B.; Software, K.A.A. and A.C.; Formal Analyses, K.A.A. J.L. and N.B.; Investigation, K.A.A. and P.A.-G.; Resources, S.C.N. L.Z. O.G. M.C.D. C.R.G. M.R.M. S.C.L. A.B. E.F.J. and A.R.; Data Curation, K.A.A.; Writing ? Original Draft, K.A.A. and S.L.B.; Writing ? Review & Editing, K.A.A. S.C.N. L.Z. O.G. P.A.-G. C.R.G. E.F.J. A.R. and S.L.B.; Visualization, K.A.A.; Funding Acquisition, K.A.A. and S.L.B. A.R. receives royalties from LGC/Biosearch Technologies related to Stellaris RNA-FISH. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = apr,
day = "15",
doi = "10.1016/j.molcel.2021.03.006",
language = "English (US)",
volume = "81",
pages = "1666--1681.e6",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "8",
}