Identification and partial characterization of new cell density-dependent nucleocytoplasmic shuttling proteins and open chromatin

Abstract The contact inhibition of proliferation (CIP) denotes the cell density-dependent inhibition of growth, and the loss of CIP represents a hallmark of cancer. However, the mechanism by which CIP regulates gene expression remains poorly understood. Chromatin is a highly complex structure consis...

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Main Authors: Kangjing Li, Yaxin Li, Fumihiko Nakamura
Format: Article
Language:English
Published: Nature Portfolio 2023-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-49100-6
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author Kangjing Li
Yaxin Li
Fumihiko Nakamura
author_facet Kangjing Li
Yaxin Li
Fumihiko Nakamura
author_sort Kangjing Li
collection DOAJ
description Abstract The contact inhibition of proliferation (CIP) denotes the cell density-dependent inhibition of growth, and the loss of CIP represents a hallmark of cancer. However, the mechanism by which CIP regulates gene expression remains poorly understood. Chromatin is a highly complex structure consisting of DNA, histones, and trans-acting factors (TAFs). The binding of TAF proteins to specific chromosomal loci regulates gene expression. Therefore, profiling chromatin is crucial for gaining insight into the gene expression mechanism of CIP. In this study, using modified proteomics of TAFs bound to DNA, we identified a protein that shuttles between the nucleus and cytosol in a cell density-dependent manner. We identified TIPARP, PTGES3, CBFB, and SMAD4 as cell density-dependent nucleocytoplasmic shuttling proteins. In low-density cells, these proteins predominantly reside in the nucleus; however, upon reaching high density, they relocate to the cytosol. Given their established roles in gene regulation, our findings propose their involvement as CIP-dependent TAFs. We also identified and characterized potential open chromatin regions sensitive to changes in cell density. These findings provide insights into the modulation of chromatin structure by CIP.
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spelling doaj.art-eee46e92976746c5853be2d5eaf14e3d2023-12-10T12:14:16ZengNature PortfolioScientific Reports2045-23222023-12-0113111510.1038/s41598-023-49100-6Identification and partial characterization of new cell density-dependent nucleocytoplasmic shuttling proteins and open chromatinKangjing Li0Yaxin Li1Fumihiko Nakamura2School of Pharmaceutical Science and Technology, Tianjin University, Nankai DistrictSchool of Pharmaceutical Science and Technology, Tianjin University, Nankai DistrictSchool of Pharmaceutical Science and Technology, Tianjin University, Nankai DistrictAbstract The contact inhibition of proliferation (CIP) denotes the cell density-dependent inhibition of growth, and the loss of CIP represents a hallmark of cancer. However, the mechanism by which CIP regulates gene expression remains poorly understood. Chromatin is a highly complex structure consisting of DNA, histones, and trans-acting factors (TAFs). The binding of TAF proteins to specific chromosomal loci regulates gene expression. Therefore, profiling chromatin is crucial for gaining insight into the gene expression mechanism of CIP. In this study, using modified proteomics of TAFs bound to DNA, we identified a protein that shuttles between the nucleus and cytosol in a cell density-dependent manner. We identified TIPARP, PTGES3, CBFB, and SMAD4 as cell density-dependent nucleocytoplasmic shuttling proteins. In low-density cells, these proteins predominantly reside in the nucleus; however, upon reaching high density, they relocate to the cytosol. Given their established roles in gene regulation, our findings propose their involvement as CIP-dependent TAFs. We also identified and characterized potential open chromatin regions sensitive to changes in cell density. These findings provide insights into the modulation of chromatin structure by CIP.https://doi.org/10.1038/s41598-023-49100-6
spellingShingle Kangjing Li
Yaxin Li
Fumihiko Nakamura
Identification and partial characterization of new cell density-dependent nucleocytoplasmic shuttling proteins and open chromatin
Scientific Reports
title Identification and partial characterization of new cell density-dependent nucleocytoplasmic shuttling proteins and open chromatin
title_full Identification and partial characterization of new cell density-dependent nucleocytoplasmic shuttling proteins and open chromatin
title_fullStr Identification and partial characterization of new cell density-dependent nucleocytoplasmic shuttling proteins and open chromatin
title_full_unstemmed Identification and partial characterization of new cell density-dependent nucleocytoplasmic shuttling proteins and open chromatin
title_short Identification and partial characterization of new cell density-dependent nucleocytoplasmic shuttling proteins and open chromatin
title_sort identification and partial characterization of new cell density dependent nucleocytoplasmic shuttling proteins and open chromatin
url https://doi.org/10.1038/s41598-023-49100-6
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AT yaxinli identificationandpartialcharacterizationofnewcelldensitydependentnucleocytoplasmicshuttlingproteinsandopenchromatin
AT fumihikonakamura identificationandpartialcharacterizationofnewcelldensitydependentnucleocytoplasmicshuttlingproteinsandopenchromatin