scholarly journals Unsupervised tensor decomposition-based method to extract candidate transcription factors as histone modification bookmarks in post-mitotic transcriptional reactivation

2020 ◽  
Author(s):  
Y-H. Taguchi ◽  
Turki Turki
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Cell Division ◽  
Histone Modification ◽  
Histone Modifications ◽  
Gene Sequence ◽  
Tensor Decomposition ◽  
Replication Stage ◽  
Transcriptional Reactivation ◽  
Unsupervised Feature Extraction

ABSTRACTThe histone group added to a gene sequence must be released during mitosis to halt transcription during the DNA replication stage of the cell cycle. However, the detailed mechanism of this transcription regulation remains unclear. In particular, it is not realistic to reconstruct all appropriate histone modifications throughout the genome from scratch after mitosis. Thus, it is reasonable to assume that there might be a type of “bookmark” that retains the positions of histone modifications, which can be readily restored after mitosis. We developed a novel computational approach comprising tensor decomposition (TD)-based unsupervised feature extraction (FE) to identify transcription factors (TFs) that bind to genes associated with reactivated histone modifications as candidate histone bookmarks. To the best of our knowledge, this is the first application of TD-based unsupervised FE to the cell division context and phases pertaining to the cell cycle in general. The candidate TFs identified with this approach were functionally related to cell division, suggesting the suitability of this method and the potential of the identified TFs as bookmarks for histone modification during mitosis.

scholarly journals Unsupervised tensor decomposition-based method to extract candidate transcription factors as histone modification bookmarks in post-mitotic transcriptional reactivation

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251032
Author(s):  
Y-h. Taguchi ◽  
Turki Turki
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Cell Division ◽  
Histone Modification ◽  
Histone Modifications ◽  
Gene Sequence ◽  
Tensor Decomposition ◽  
Replication Stage ◽  
Transcriptional Reactivation ◽  
Unsupervised Feature Extraction

The histone group added to a gene sequence must be removed during mitosis to halt transcription during the DNA replication stage of the cell cycle. However, the detailed mechanism of this transcription regulation remains unclear. In particular, it is not realistic to reconstruct all appropriate histone modifications throughout the genome from scratch after mitosis. Thus, it is reasonable to assume that there might be a type of “bookmark” that retains the positions of histone modifications, which can be readily restored after mitosis. We developed a novel computational approach comprising tensor decomposition (TD)-based unsupervised feature extraction (FE) to identify transcription factors (TFs) that bind to genes associated with reactivated histone modifications as candidate histone bookmarks. To the best of our knowledge, this is the first application of TD-based unsupervised FE to the cell division context and phases pertaining to the cell cycle in general. The candidate TFs identified with this approach were functionally related to cell division, suggesting the suitability of this method and the potential of the identified TFs as bookmarks for histone modification during mitosis.

Geminin Regulates Hematopoietic Stem Cell Proliferation and Differentiation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1478-1478
Author(s):  
Kathryn M. Shinnick ◽  
Kelly A. Barry ◽  
Elizabeth A. Eklund ◽  
Thomas J. McGarry
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Transcription Factors ◽  
Cell Division ◽  
Dna Replication ◽  
Hematopoietic Stem Cells ◽  
Conflicts Of Interest ◽  
Regulatory Protein ◽  
Hematopoietic Stem ◽  
Proliferation And Differentiation

Abstract Abstract 1478 Poster Board I-501 Hematopoietic stem cells supply the circulation with mature blood cells throughout life. Progenitor cell division and differentiation must be carefully balanced in order to supply the proper numbers and proportions of mature cells. The mechanisms that control the choice between continued cell division and terminal differentiation are incompletely understood. The unstable regulatory protein Geminin is thought to maintain cells in an undifferentiated state while they proliferate. Geminin is a bi-functional protein. It limits the extent of DNA replication to one round per cell cycle by binding and inhibiting the essential replication factor Cdt1. Loss of Geminin leads to replication abnormalities that activate the DNA replication checkpoint and the Fanconi Anemia (FA) pathway. Geminin also influences patterns of cell differentiation by interacting with Homeobox (Hox) transcription factors and chromatin remodeling proteins. To examine how Geminin affects the proliferation and differentiation of hematopoietic stem cells, we created a mouse strain in which Geminin is deleted from the proliferating cells of the bone marrow. Geminin deletion has profound effects on all three hematopoietic lineages. The production of mature erythrocytes and leukocytes is drastically reduced and the animals become anemic and neutropenic. In contrast, the population of megakaryocytes is dramatically expanded and the animals develop thrombocytosis. Interestingly, the number of c-Kit+ Sca1+ Lin- (KSL) stem cells is maintained, at least in the short term. Myeloid colony forming cells are also preserved, but the colonies that grow are smaller. We conclude that Geminin deletion causes a maturation arrest in some lineages and directs cells down some differentiation pathways at the expense of others. We are now testing how Geminin loss affects cell cycle checkpoint pathways, whether Geminin regulates hematopoietic transcription factors, and whether Geminin deficient cells give rise to leukemias or lymphomas. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Whi5 and Stb1 define redundant pathways through which the G1 cyclin Cln3 promotes cell division

2021 ◽  
Author(s):  
Sangeet Honey ◽  
Bruce Futcher
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factors ◽  
Cell Division ◽  
Transcriptional Repression ◽  
Phosphorylation Site ◽  
Phosphorylation Sites ◽  
G1 Cyclin ◽  
Cdk Phosphorylation ◽  
Commitment To Cell Division

In the budding yeast S. cerevisiae, commitment to cell division, Start, is promoted by a trio of G1 cyclins, Cln1, Cln2, and Cln3, that activate the CDK kinase Cdc28. The active kinases somehow activate two transcription factors, SBF and MBF, leading to induction of about 100 genes for budding, DNA synthesis, and other early cell cycle processes. Activation of the transcription factors is opposed by a repressive protein called Whi5, and also by a second repressive protein called Stb1. Both Whi5 and Stb1 contain many potential sites for phosphorylation by CDK kinase, and is thought that relief of transcriptional repression involves the phosphorylation of Whi5 and Stb1 by CDK. Phosphorylation site mutants have been studied for Whi5, but not for Stb1. Here, we create phosphorylation site mutants of Stb1, and combine them with site mutants of Whi5. We find that the G1 cyclin Cln3 activates cell cycle transcription effectively when at least one of these proteins has its phosphorylation sites. However, when both Whi5 and Stb1 simultaneously lack all consensus phosphorylation sites, Cln3 is unable, or almost unable, to induce any gene expression, or any advancement of Start. Thus the G1 cyclin signaling pathway to Start has a requirement for CDK phosphorylation sites on either Whi5 or Stb1.

scholarly journals Quantitative model of eukaryotic Cdk control through the Forkhead CONTROLLER

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Matteo Barberis
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Cell Division ◽  
Design Principle ◽  
Budding Yeast ◽  
Eukaryotic Cell ◽  
Quantitative Model ◽  
Sequential Order ◽  
Forkhead Transcription Factors

AbstractIn budding yeast, synchronization of waves of mitotic cyclins that activate the Cdk1 kinase occur through Forkhead transcription factors. These molecules act as controllers of their sequential order and may account for the separation in time of incompatible processes. Here, a Forkhead-mediated design principle underlying the quantitative model of Cdk control is proposed for budding yeast. This design rationalizes timing of cell division, through progressive and coordinated cyclin/Cdk-mediated phosphorylation of Forkhead, and autonomous cyclin/Cdk oscillations. A “clock unit” incorporating this design that regulates timing of cell division is proposed for both yeast and mammals, and has a DRIVER operating the incompatible processes that is instructed by multiple CLOCKS. TIMERS determine whether the clocks are active, whereas CONTROLLERS determine how quickly the clocks shall function depending on external MODULATORS. This “clock unit” may coordinate temporal waves of cyclin/Cdk concentration/activity in the eukaryotic cell cycle making the driver operate the incompatible processes, at separate times.

scholarly journals CDK4/6 regulate lysosome biogenesis through TFEB/TFE3

2020 ◽  
Vol 219 (8) ◽  
Author(s):  
Qiuyuan Yin ◽  
Youli Jian ◽  
Meng Xu ◽  
Xiahe Huang ◽  
Niya Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Cell Division ◽  
Nuclear Export ◽  
Cyclin D ◽  
Cyclin Dependent Kinases ◽  
Genetic Inactivation ◽  
Lysosome Biogenesis ◽  
Molecular Events ◽  
Signaling Organelles

Lysosomes are degradation and signaling organelles that adapt their biogenesis to meet many different cellular demands; however, it is unknown how lysosomes change their numbers for cell division. Here, we report that the cyclin-dependent kinases CDK4/6 regulate lysosome biogenesis during the cell cycle. Chemical or genetic inactivation of CDK4/6 increases lysosomal numbers by activating the lysosome and autophagy transcription factors TFEB and TFE3. CDK4/6 interact with and phosphorylate TFEB/TFE3 in the nucleus, thereby inactivating them by promoting their shuttling to the cytoplasm. During the cell cycle, lysosome numbers increase in S and G2/M phases when cyclin D turnover diminishes CDK4/6 activity. These findings not only uncover the molecular events that direct the nuclear export of TFEB/TFE3, but also suggest a mechanism that controls lysosome biogenesis in the cell cycle. CDK4/6 inhibitors promote autophagy and lysosome-dependent degradation, which has important implications for the therapy of cancer and lysosome-related disorders.

scholarly journals Identification of Transcription Factors, Biological Pathways, and Diseases as Mediated by N6-methyladenosine Using Tensor Decomposition-Based Unsupervised Feature Extraction

2020 ◽  
Vol 11 (1) ◽  
pp. 213
Author(s):  
Y-h. Taguchi ◽  
S. Akila Parvathy Dharshini ◽  
M. Michael Gromiha
Keyword(s):  
Feature Extraction ◽  
Transcription Factors ◽  
Human Cancer ◽  
Embryonic Stem ◽  
Cancer Cell Line ◽  
Tensor Decomposition ◽  
Rna Modification ◽  
Biological Processes ◽  
Gene Sets ◽  
Unsupervised Feature Extraction

N6-methyladenosine (m6A) editing is the most common RNA modification known to contribute to various biological processes. Nevertheless, the mechanism by which m6A regulates transcription is unclear. Recently, it was proposed that m6A controls transcription through histone modification, although no comprehensive analysis using this dataset was performed. In this study, we applied tensor decomposition (TD)-based unsupervised feature extraction (FE) to a dataset composed of mouse embryonic stem cells (mESC) and a human cancer cell line (HEC-1-A) and successfully identified two sets of genes significantly overlapping between humans and mice (63 significantly overlapped genes among a total of 16,763 genes common to the two species). These significantly overlapped genes occupy at most 10% genes from both gene sets. Using these two sets of genes, we identified transcription factors (TFs) that m6A might recruit, biological processes that m6A might contribute to, and diseases that m6A might cause; they also largely overlap with each other. Since they were commonly identified using two independent datasets, the results regarding these TFs, biological processes, and diseases should be highly robust and trustworthy. It will help us to understand the mechanisms by which m6A contributes to biological processes.

Phosphoinositide 3-kinase and Forkhead, a switch for cell division

2004 ◽  
Vol 32 (2) ◽  
pp. 360-361 ◽  
Author(s):  
L. Martínez-Gac ◽  
B. Álvarez ◽  
Z. García ◽  
M. Marqués ◽  
M. Arrizabalaga ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Cell Division ◽  
Cell Growth ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Downstream Effector ◽  
Cell Cycle Entry ◽  
Foxo Transcription Factors ◽  
Phosphoinositide 3 Kinase

Cell cycle progression is a tightly controlled process. To initiate cell division, mitogens trigger a number of early signals that promote the G0–G1 transition by inducing cell growth and the activation of G1 cyclins. Activation of cyclin E/cdk2 (cyclin-dependent kinase 2) at the end of G1 is then required to trigger DNA synthesis (S phase entry). Among the early signals induced by mitogens, activation of PI3K (phosphoinositide 3-kinase) appears essential to induce cell cycle entry, as it regulates cell growth signalling pathways, which in turn determine the rate of cell cycle progression. Another mechanisms by which PI3K and its downstream effector protein kinase B regulate cell cycle entry is by inactivation of the FOXO (Forkhead Box, subgroup O) transcription factors, which induce expression of quiescence genes such as those encoding p27kip, p130 and cyclin G2. PI3K/FOXO then work as a complementary switch: when PI3K is active, FOXO transcription factors are inactive. The switch is turned on and off at different phases of the cell cycle, thus regulating cell cycle progression.

scholarly journals Cell Cycle Regulation by Heat Shock Transcription Factors

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 203
Author(s):  
Yasuko Tokunaga ◽  
Ken-Ichiro Otsuyama ◽  
Naoki Hayashida
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Cell Division ◽  
Heat Shock ◽  
Cell Cycle Regulation ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Heat Shock Transcription Factors ◽  
Gene Bookmarking ◽  
Cycle Regulation

Cell division and cell cycle mechanism has been studied for 70 years. This research has revealed that the cell cycle is regulated by many factors, including cyclins and cyclin-dependent kinases (CDKs). Heat shock transcription factors (HSFs) have been noted as critical proteins for cell survival against various stresses; however, recent studies suggest that HSFs also have important roles in cell cycle regulation-independent cell-protective functions. During cell cycle progression, HSF1, and HSF2 bind to condensed chromatin to provide immediate precise gene expression after cell division. This review focuses on the function of these HSFs in cell cycle progression, cell cycle arrest, gene bookmarking, mitosis and meiosis.

scholarly journals Cell cycle regulated transcription: from yeast to cancer

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 877 ◽  
Author(s):  
Christopher J. McInerny
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Transcription Factors ◽  
Cell Division ◽  
Model Systems ◽  
Gene Products ◽  
Control Of Gene Expression ◽  
Forkhead Transcription Factors ◽  
Fundamental Process

Recent studies have revealed exciting new functions for forkhead transcription factors in cell proliferation and development. Cell proliferation is a fundamental process controlled by multiple overlapping mechanisms, and the control of gene expression plays a major role in the orderly and timely division of cells. This occurs through transcription factors regulating the expression of groups of genes at particular phases of the cell division cycle. In this way, the encoded gene products are present when they are required. This review outlines recent advances in our understanding of this process in yeast model systems and describes how this knowledge has informed analysis in more developmentally complex eukaryotes, particularly where it is relevant to human disease.

Sign in / Sign up

Export Citation Format

Share Document