scholarly journals Formation and recycling of an active epigenetic mark mediated by cell cycle-specific RNAs

2021 ◽  
Author(s):  
Daniel Geoffrey Tenen ◽  
Vladimir Espinosa Angarica ◽  
Dennis Kappei ◽  
Danielle Tenen ◽  
Emanuele Monteleone . ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Noncoding Rnas ◽  
S Phase ◽  
Long Noncoding Rnas ◽  
Epigenetic Mark ◽  
Histone Acetyl Transferase ◽  
Regulatory Regions ◽  
Epigenetic Marks ◽  
Gene Regulatory ◽  
Active Genes

The mechanisms by which epigenetic modifications are established in gene regulatory regions of active genes remain poorly understood. The data presented show that the establishment and recycling of a major epigenetic mark, the acetylated form of the replacement histone H2A.Z, is regulated by cell cycle-specific long noncoding RNAs encoded in regions adjacent to the promoters of active genes. These transcripts, termed SPEARs (S Phase EArly RNAs), are induced in early S phase: their expression precedes that of the downstream genes on which they exert their regulatory action. SPEARs drive the modification and deposition of the acetylated form of histone H2A.Z by bringing together the replacement histone and the histone acetyl transferase TIP60. This widespread bimodal pathway constitutes a novel RNA-mediated mechanism for the establishment of epigenetic marks and cell-specific epigenetic profiles, thereby providing a unifying explanation for the accuracy and persistence of epigenetic marks on chromatin.

scholarly journals Formation and recycling of an active epigenetic mark mediated by cell cycle-specific RNAs

2021 ◽  
Author(s):  
Daniel Tenen ◽  
Alexander Ebralidze ◽  
Vladimir Angarica ◽  
Yanjing Liu ◽  
Dennis Kappei ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Noncoding Rnas ◽  
S Phase ◽  
Long Noncoding Rnas ◽  
Epigenetic Mark ◽  
Histone Acetyl Transferase ◽  
Regulatory Regions ◽  
Epigenetic Marks ◽  
Gene Regulatory ◽  
Active Genes

Abstract The mechanisms by which epigenetic modifications are established in gene regulatory regions of active genes remain poorly understood. The data presented show that the establishment and recycling of a major epigenetic mark, the acetylated form of the replacement histone H2A.Z, is regulated by cell cycle-specific long noncoding RNAs encoded in regions adjacent to the promoters of active genes. These transcripts, termed SPEARs (S Phase EArly RNAs), are induced in early S phase: their expression precedes that of the downstream genes on which they exert their regulatory action. SPEARs drive the modification and deposition of the acetylated form of histone H2A.Z by bringing together the replacement histone and the histone acetyl transferase TIP60. This widespread bimodal pathway constitutes a novel RNA-mediated mechanism for the establishment of epigenetic marks and cell-specific epigenetic profiles, thereby providing a unifying explanation for the accuracy and persistence of epigenetic marks on chromatin.

scholarly journals Cdk Phosphorylation of a Nucleoporin Controls Localization of Active Genes through the Cell Cycle

2010 ◽  
Vol 21 (19) ◽  
pp. 3421-3432 ◽  
Author(s):  
Donna Garvey Brickner ◽  
Jason H. Brickner
Keyword(s):  
Cell Cycle ◽  
Nuclear Periphery ◽  
S Phase ◽  
Nuclear Pore ◽  
Cdk Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Initiation Of Dna Replication ◽  
Cdk Phosphorylation ◽  
Inducible Genes ◽  
Active Genes

Many inducible genes in yeast are targeted to the nuclear pore complex when active. We find that the peripheral localization of the INO1 and GAL1 genes is regulated through the cell cycle. Active INO1 and GAL1 localized at the nuclear periphery during G1, became nucleoplasmic during S-phase, and then returned to the nuclear periphery during G2/M. Loss of peripheral targeting followed the initiation of DNA replication and was lost in cells lacking a cyclin-dependent kinase (Cdk) inhibitor. Furthermore, the Cdk1 kinase and two Cdk phosphorylation sites in the nucleoporin Nup1 were required for peripheral targeting of INO1 and GAL1. Introduction of aspartic acid residues in place of either of these two sites in Nup1 bypassed the requirement for Cdk1 and resulted in targeting of INO1 and GAL1 to the nuclear periphery during S-phase. Thus, phosphorylation of a nuclear pore component by cyclin dependent kinase controls the localization of active genes to the nuclear periphery through the cell cycle.

scholarly journals Long Noncoding RNA Rps4l Mediates the Proliferation of Hypoxic Pulmonary Artery Smooth Muscle Cells

Hypertension ◽  
2020 ◽  
Vol 76 (4) ◽  
pp. 1124-1133 ◽  
Author(s):  
Ying Liu ◽  
Hongyue Zhang ◽  
Yiying Li ◽  
Lixin Yan ◽  
Wei Du ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Smooth Muscle Cells ◽  
Vascular Remodeling ◽  
Cell Cycle Progression ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Cycle Progression ◽  
Pulmonary Artery Smooth Muscle

Pulmonary hypertension (PH) is a rare and fatal disorder involving the vascular remodeling of pulmonary arteries mediated by the enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs). Long noncoding RNAs are a subclass of regulatory molecules with diverse cellular functions, but their role in PH remains largely unexplored. We aimed to identify and determine the functions of long noncoding RNAs involved in hypoxia-induced PH and PASMC proliferation. RNA sequencing in a hypoxic mouse model identified hypoxia-regulated long noncoding RNAs, including Rps4l. Rps4l expression was significantly reduced in PH-model mice and hypoxic PASMCs. The subcellular localization of Rps4l was detected by RNA fluorescence in situ hybridization and quantification of nuclear/cytoplasmic RNA. Rps4l overexpression rescued pulmonary arterial hypertension features, as demonstrated by right ventricle hypertrophy, right ventricular systolic pressure, hemodynamics, cardiac function, and vascular remodeling. At the cellular level, Rps4l overexpression weakened cell viability and proliferation and suppressed cell cycle progression. Potential Rps4l-binding proteins were identified via RNA pull-down followed by mass spectrometry, RNA immunoprecipitation, and microscale thermophoresis. These results indicated that Rps4l is associated with and affects the stabilization of ILF3 (interleukin enhancer-binding factor 3). Rps41 further regulates the levels of HIF-1α and consequently leads to hypoxia-induced PASMC proliferation and migration. Our results showed that in hypoxic PASMCs, Rps4l expression decreases due to regulation by hypoxia. This decrease affects the proliferation, migration, and cell cycle progression of PASMCs through ILF3/HIF-1α. These results provide a theoretical basis for further investigations into the pathological mechanism of hypoxic PH and may provide insight for the development of novel treatments.

scholarly journals Cisplatin induces HepG2 cell cycle arrest through targeting specific long noncoding RNAs and the p53 signaling pathway

2016 ◽  
Vol 12 (6) ◽  
pp. 4605-4612 ◽  
Author(s):  
Ping Wang ◽  
Jiayue Cui ◽  
Jihong Wen ◽  
Yunhui Guo ◽  
Liangzi Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Hepg2 Cell ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
P53 Signaling ◽  
Cycle Arrest ◽  
P53 Signaling Pathway

scholarly journals Role of MYC-Regulated Long Noncoding RNAs in Cell Cycle Regulation and Tumorigenesis

2015 ◽  
Vol 107 (4) ◽  
Author(s):  
Taewan Kim ◽  
Young-Jun Jeon ◽  
Ri Cui ◽  
Ji-Hoon Lee ◽  
Yong Peng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Cycle Regulation

scholarly journals Localization and expression of mRNA for a macronuclear-specific histone H2A variant (hv1) during the cell cycle and conjugation of Tetrahymena thermophila.

1988 ◽  
Vol 8 (11) ◽  
pp. 4780-4786 ◽  
Author(s):  
E M White ◽  
M A Gorovsky
Keyword(s):  
Cell Cycle ◽  
In Situ Hybridization ◽  
S Phase ◽  
Histone H2a ◽  
Mrna Accumulation ◽  
Macronuclear Development ◽  
A Cell ◽  
Size And Morphology ◽  
Active Genes

hv1 is a histone H2A variant found in the transcriptionally active Tetrahymena macronucleus but not in the transcriptionally inert micronucleus. This, along with a number of other lines of evidence, suggests that hv1 is associated with active genes. We have used a cDNA clone as a probe to study hv1 mRNA accumulation throughout the cell cycle and during conjugation. In situ hybridization to glutaraldehyde-fixed growing cells, whose position in the cell cycle was determined by size and morphology, showed that hv1 message is present throughout the cell cycle. The message was uniformly distributed in these vegetative cells. Compared with four other Tetrahymena histone genes studied to date (S. -M. Yu, S. Horowitz, and M. A. Gorovsky, Genes Dev., 1:683, 1987; M. Wu, C. D. Allis, and M. A. Gorovsky, Proc. Natl. Acad. Sci. USA 85:2205, 1988), hv1 mRNA is the only one that does not show a pattern of accumulation during the cell cycle that could explain the nuclear localization of its encoded protein. Thus, either hv1 or some molecule with which it associates contains a macronuclear-specific targeting sequence or there exists a cell cycle-regulated event that restricts its translation to the macronuclear S phase. In situ hybridization to conjugating cells revealed that hv1 message amounts increase just prior to macronuclear development and decline precipitously after the cells separate. The hv1 message showed no marked subcellular localization and is, therefore, unlikely to play a role in the cytoplasmic determination known to occur during macronuclear development.

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