Negative Regulation of p21Waf1/Cip1 by Human INO80 Chromatin Remodeling Complex Is Implicated in Cell Cycle Phase G2/M Arrest and Abnormal Chromosome Stability

PloS One
Lingling CaoYong Cai

Abstract

We previously identified an ATP-dependent human Ino80 (INO80) chromatin remodeling complex which shares a set of core subunits with yeast Ino80 complex. Although research evidence has suggested that INO80 complex functions in gene transcription and genome stability, the precise mechanism remains unclear. Herein, based on gene expression profiles from the INO80 complex-knockdown in HeLa cells, we first demonstrate that INO80 complex negatively regulates the p21Waf1/Cip1 (p21) expression in a p53-mediated mechanism. In chromatin immunoprecipitation (ChIP) and a sequential ChIP (Re-ChIP) assays, we determined that the INO80 complex and p53 can bind to the same promoter region of p21 gene (-2.2 kb and -1.0 kb upstream of the p21 promoter region), and p53 is required for the recruitment of the INO80 complex to the p21 promoter. RNAi knockdown strategies of INO80 not only led to prolonged progression of cell cycle phase G2/M to G1, but it also resulted in abnormal chromosome stability. Interestingly, high expression of p21 was observed in most morphologically-changed cells, suggesting that negative regulation of p21 by INO80 complex might be implicated in maintaining the cell cycle process and chromosome stability. Together, our find...Continue Reading

References

Jan 1, 1992·Annual Review of Biochemistry·C Norbury, P Nurse
Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Dec 16, 1993·Nature·Y XiongD Beach
Dec 10, 1998·Nucleic Acids Research·H OgataM Kanehisa
Oct 19, 2005·The Journal of Biological Chemistry·Jingji JinJoan Weliky Conaway
Nov 1, 2005·Trends in Biochemical Sciences·Jingji JinThomas Kusch
Apr 25, 2006·Molecular Biotechnology·George R Stark, William R Taylor
Aug 3, 2007·Genes & Development·Nicolas GévryLuc Gaudreau
Aug 28, 2007·Nature Structural & Molecular Biology·Yong CaiJoan W Conaway
Apr 15, 2008·Current Biology : CB·Kenji ShimadaSusan M Gasser
Dec 9, 2008·Trends in Biochemical Sciences·Ronald C Conaway, Joan Weliky Conaway
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Apr 10, 2009·Annual Review of Biochemistry·Cedric R Clapier, Bradley R Cairns
Mar 20, 2010·Cellular and Molecular Life Sciences : CMLS·Shin-Kyoung HurJongbum Kwon
Mar 23, 2010·Current Opinion in Cell Biology·Vincent DionSusan M Gasser
Sep 3, 2010·Current Opinion in Cell Biology·Vassilis G Gorgoulis, Thanos D Halazonetis
Oct 26, 2010·Biochemical and Biophysical Research Communications·Shu-ichiro KashiwabaYasufumi Murakami
Nov 26, 2010·Apoptosis : an International Journal on Programmed Cell Death·Fei WangYunfeng Zhao
Apr 20, 2011·Cold Spring Harbor Symposia on Quantitative Biology·S Watanabe, C L Peterson
Aug 5, 2011·Journal of Cellular Biochemistry·Jana Cmielová, M Rezáčová
Nov 14, 2012·Mechanisms of Ageing and Development·Kangmoon LeeJeong Hyeon Park
Nov 20, 2012·Current Opinion in Oncology·Noel A Warfel, Wafik S El-Deiry
Jan 29, 2013·Current Opinion in Genetics & Development·Andrew SeeberSusan M Gasser
Jul 3, 2013·Nature Communications·Gwendolyn BennettCraig L Peterson
Jul 14, 2014·Nucleic Acids Research·Ivelina VassilevaBoyka Anachkova
Aug 5, 2014·Trends in Cell Biology·Christian B Gerhold, Susan M Gasser

❮ Previous
Next ❯

Citations

Dec 13, 2016·American Journal of Human Genetics·Dong-Chuan GuoDianna M Milewicz
Jan 18, 2017·Mutagenesis·Luíza Araújo da Costa XavierViviane Souza do Amaral
Sep 10, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Li-Qin ChengDe-Pei Liu
Aug 30, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Jérôme PoliManolis Papamichos-Chronakis
May 1, 2019·International Journal of Molecular Sciences·Yi SuiJingji Jin

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE68655

Methods Mentioned

BETA
electron microscopy
ChIP
transfection
electrophoresis
PCR
flow cytometry
Immunoprecipitation
transfections
ChIPs

Software Mentioned

Genomestudio
DAVID ( Database for Annotation , Visualization and Integrated...
DAVID
ModFit LT
Quantity One Basic
Illumina

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.

Cancer Epigenetics and Chromatin (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin and its role in cancer epigenetics please follow this feed to learn more.

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Cancer Epigenetics Chromatin Complexes (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin complexes and their role in cancer epigenetics.