TY - JOUR
T1 - NcRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs
AU - Yang, Liuqing
AU - Lin, Chunru
AU - Liu, Wen
AU - Zhang, Jie
AU - Ohgi, Kenneth A.
AU - Grinstein, Jonathan D.
AU - Dorrestein, Pieter C.
AU - Rosenfeld, Michael G.
N1 - Funding Information:
We thank C. Nelson for assistance with cell culture; J. Hightower for artwork; D. Benson, M. Fisher, and R. Pardee for assistance with the manuscript; Dr. B. Tanasa for providing E2F1 target sites from previously published ChIP-Seq data; Dr. P. Sun and Dr. R. Liao for providing BJ cells and technical support for the senescence study; Dr. R. June for assistance with flow cytometry analysis; and Dr. M. Ghassemian and Wei Ting Liu for mass spectrometry analysis. Michael G. Rosenfeld is a Howard Hughes Medical Institute Investigator. This study was funded by grants from DK018477, DK74868, DK39949, CA97134, NS34934, W81XWH-08-1-0665, and the Prostate Cancer Foundation to M.G.R.; L.Y. is the recipient of a DoD Era of Hope Postdoctoral Award (W81XWH-08-1-0554); and C.L. is the recipient of a Susan G. Komen for the Cure Fellowship (KG080247).
PY - 2011/11/11
Y1 - 2011/11/11
N2 - Although eukaryotic nuclei contain distinct architectural structures associated with noncoding RNAs (ncRNAs), their potential relationship to regulated transcriptional programs remains poorly understood. Here, we report that methylation/demethylation of Polycomb 2 protein (Pc2) controls relocation of growth-control genes between Polycomb bodies (PcGs) and interchromatin granules (ICGs) in response to growth signals. This movement is the consequence of binding of methylated and unmethylated Pc2 to the ncRNAs TUG1 and MALAT1/NEAT2, located in PcGs and ICGs, respectively. These ncRNAs mediate assembly of multiple corepressors/coactivators and can serve to switch mark recognition by "readers" of the histone code. Additionally, binding of NEAT2 to unmethylated Pc2 promotes E2F1 SUMOylation, leading to activation of the growth-control gene program. These observations delineate a molecular pathway linking the actions of subnuclear structure-specific ncRNAs and nonhistone protein methylation to relocation of transcription units in the three-dimensional space of the nucleus, thus achieving coordinated gene expression programs. PaperClip:
AB - Although eukaryotic nuclei contain distinct architectural structures associated with noncoding RNAs (ncRNAs), their potential relationship to regulated transcriptional programs remains poorly understood. Here, we report that methylation/demethylation of Polycomb 2 protein (Pc2) controls relocation of growth-control genes between Polycomb bodies (PcGs) and interchromatin granules (ICGs) in response to growth signals. This movement is the consequence of binding of methylated and unmethylated Pc2 to the ncRNAs TUG1 and MALAT1/NEAT2, located in PcGs and ICGs, respectively. These ncRNAs mediate assembly of multiple corepressors/coactivators and can serve to switch mark recognition by "readers" of the histone code. Additionally, binding of NEAT2 to unmethylated Pc2 promotes E2F1 SUMOylation, leading to activation of the growth-control gene program. These observations delineate a molecular pathway linking the actions of subnuclear structure-specific ncRNAs and nonhistone protein methylation to relocation of transcription units in the three-dimensional space of the nucleus, thus achieving coordinated gene expression programs. PaperClip:
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U2 - 10.1016/j.cell.2011.08.054
DO - 10.1016/j.cell.2011.08.054
M3 - Article
C2 - 22078878
AN - SCOPUS:81055140863
SN - 0092-8674
VL - 147
SP - 773
EP - 788
JO - Cell
JF - Cell
IS - 4
ER -