scholarly journals Unveiling E2F4, TEAD1 and AP-1 as regulatory transcription factors of the replicative senescence program by multi-omics analysis

2022 ◽  
Author(s):  
Yuting Wang ◽  
Liping Liu ◽  
Yifan Song ◽  
Xiaojie Yu ◽  
Hongkui Deng
Keyword(s):  
Transcription Factors ◽  
Replicative Senescence ◽  
Stable State ◽  
Mouse Skin ◽  
Proliferative Capacity ◽  
Time Resolved ◽  
Reduced Representation ◽  
Genetic Manipulations ◽  
Omics Analysis ◽  
Senescence Program

AbstractSenescence, a stable state of growth arrest, affects many physiological and pathophysiological processes, especially aging. Previous work has indicated that transcription factors (TFs) play a role in regulating senescence. However, a systematic study of regulatory TFs during replicative senescence (RS) using multi-omics analysis is still lacking. Here, we generated time-resolved RNA-seq, reduced representation bisulfite sequencing (RRBS) and ATAC-seq datasets during RS of mouse skin fibroblasts, which demonstrated that an enhanced inflammatory response and reduced proliferative capacity were the main characteristics of RS in both the transcriptome and epigenome. Through integrative analysis and genetic manipulations, we found that transcription factors E2F4, TEAD1 and AP-1 are key regulators of RS. Overexpression of E2f4 improved cellular proliferative capacity, attenuated SA-β-Gal activity and changed RS-associated differentially methylated sites (DMSs). Moreover, knockdown of Tead1 attenuated SA-β-Gal activity and partially altered the RS-associated transcriptome. In addition, knockdown of Atf3, one member of AP-1 superfamily TFs, reduced Cdkn2a (p16) expression in pre-senescent fibroblasts. Taken together, the results of this study identified transcription factors regulating the senescence program through multi-omics analysis, providing potential therapeutic targets for anti-aging.

scholarly journals Genetic interrogation of replicative senescence uncovers a dual role for USP28 in coordinating the p53 and GATA4 branches of the senescence program

2017 ◽  
Vol 31 (19) ◽  
pp. 1933-1938 ◽  
Author(s):  
Anna E. Mazzucco ◽  
Agata Smogorzewska ◽  
Chanhee Kang ◽  
Ji Luo ◽  
Michael R. Schlabach ◽  
...  
Keyword(s):  
Replicative Senescence ◽  
Dual Role ◽  
Senescence Program

scholarly journals Corrigendum: Genetic interrogation of replicative senescence uncovers a dual role for USP28 in coordinating the p53 and GATA4 branches of the senescence program

2017 ◽  
Vol 31 (22) ◽  
pp. 2310-2310
Author(s):  
Anna E. Mazzucco ◽  
Agata Smogorzewska ◽  
Chanhee Kang ◽  
Ji Luo ◽  
Michael R. Schlabach ◽  
...  
Keyword(s):  
Replicative Senescence ◽  
Dual Role ◽  
Senescence Program

scholarly journals The Transcriptional Control of Lymphatic Vascular Development

Physiology ◽  
2011 ◽  
Vol 26 (3) ◽  
pp. 146-155 ◽  
Author(s):  
Mathias Francois ◽  
Natasha L. Harvey ◽  
Benjamin M. Hogan
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Transcriptional Control ◽  
Molecular Mechanisms ◽  
Developmental Process ◽  
Vascular Development ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cell ◽  
Transcriptional Networks ◽  
Genetic Manipulations

More than 100 years ago, Florence Sabin suggested that lymphatic vessels develop by sprouting from preexisting blood vessels, but it is only over the past decade that the molecular mechanisms underpinning lymphatic vascular development have begun to be elucidated. Genetic manipulations in mice have identified a transcriptional hub comprised of Prox1, CoupTFII, and Sox18 that is essential for lymphatic endothelial cell fate specification. Recent work has identified a number of additional transcription factors that regulate later stages of lymphatic vessel differentiation and maturation. This review highlights recent advances in our understanding of the transcriptional control of lymphatic vascular development and reflects on efforts to better understand the activities of transcriptional networks during this discrete developmental process. Finally, we highlight the transcription factors associated with human lymphatic vascular disorders, demonstrating the importance of understanding how the activity of these key molecules is regulated, with a view toward the development of innovative therapeutic avenues.

Replicative Senescence, Aging and Growth-Regulatory Transcription Factors

Neurosignals ◽  
1996 ◽  
Vol 5 (3) ◽  
pp. 154-162 ◽  
Author(s):  
Goberdhan P. Dimri ◽  
A. Testori ◽  
Meileen Acosta ◽  
Judith Campisi
Keyword(s):  
Transcription Factors ◽  
Replicative Senescence

scholarly journals Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis

Oncogene ◽  
1999 ◽  
Vol 18 (52) ◽  
pp. 7423-7431 ◽  
Author(s):  
Irina V Budunova ◽  
Paloma Perez ◽  
Valerie R Vaden ◽  
Vladimir S Spiegelman ◽  
Thomas J Slaga ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Mouse Skin ◽  
Skin Carcinogenesis ◽  
Constitutive Activation

scholarly journals Insights into regulation of C2 and C4 photosynthesis in Amaranthaceae/Chenopodiaceae using RNA-Seq

2021 ◽  
Author(s):  
Christian Siadjeu ◽  
Maximilian Lauterbach ◽  
Gudrun Kadereit
Keyword(s):  
Transcription Factors ◽  
Transcriptome Analysis ◽  
C4 Photosynthesis ◽  
Stable State ◽  
Comparative Transcriptome ◽  
Rna Seq ◽  
C4 Species ◽  
Genes Encoding ◽  
C4 Evolution ◽  
Core Genes

Amaranthaceae (incl. Chenopodiaceae) show an immense diversity of C4 syndromes. More than 15 independent origins of C4 photosynthesis, partly in halophytic and/or succulent lineages, and the largest number of C4 species in eudicots signify the importance of this angiosperm lineage in C4 evolution. Here, we conduct RNA-Seq followed by comparative transcriptome analysis of three species from Camphorosmeae representing related clades with different photosynthetic types: Threlkeldiadiffusa (C3), Sedobassiasedoides (C2), and Bassiaprostrata (C4). Results show that B.prostrata belongs to the NADP–ME type and core genes encoding for C4 cycle are significantly up–regulated when compared to Sed.sedoides and T.diffusa, Sedobassiasedoides and B.prostrata share a number of up–regulated C4–related genes, however, two C4 transporters (DIT and TPT) are found significantly up–regulated only in Sed. sedoides. Combined analysis of transcription factors (TFs) of the closely related lineages (Camphorosmeae and Salsoleae) revealed that no C3 specific TFs is higher in C2 species as compared to C4 species, instead the C2 species show their own set of up–regulated TFs. Taken together, our study indicates that the hypothesis of the C2 photosynthesis as a proxy towards C4 photosynthesis is questionable in Sed.sedoides and more in favour of an independent evolutionary stable–state.

scholarly journals Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming

2017 ◽  
Author(s):  
Ralph Stadhouders ◽  
Enrique Vidal ◽  
François Serra ◽  
Bruno Di Stefano ◽  
François Le Dily ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Transcription Factors ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Time Resolved ◽  
Genome Reorganization ◽  
Chromosomal Architecture ◽  
Dynamic Interplay ◽  
Pluripotency Genes

ABSTRACTChromosomal architecture is known to influence gene expression, yet its role in controlling cell fate remains poorly understood. Reprogramming of somatic cells into pluripotent stem cells by the transcription factors (TFs) Oct4, Sox2, Klf4 and Myc offers an opportunity to address this question but is severely limited by the low proportion of responding cells. We recently developed a highly efficient reprogramming protocol that synchronously converts somatic into pluripotent stem cells. Here, we employ this system to integrate time-resolved changes in genome topology with gene expression, TF binding and chromatin state dynamics. This revealed that TFs drive topological genome reorganization at multiple architectural levels, which often precedes changes in gene expression. Removal of locus-specific topological barriers can explain why pluripotency genes are activated sequentially, instead of simultaneously, during reprogramming. Taken together, our study implicates genome topology as an instructive force for implementing transcriptional programs and cell fate in mammals.

scholarly journals SOX transcription factors direct TCF-independent WNT/beta-catenin transcription.

2021 ◽  
Author(s):  
Shreyasi Mukherjee ◽  
David M Luedeke ◽  
Leslie Brown ◽  
Aaron Zorn
Keyword(s):  
Transcription Factors ◽  
Tissue Regeneration ◽  
Pluripotent Stem Cells ◽  
Target Genes ◽  
Fundamental Question ◽  
Beta Catenin ◽  
Cell Type ◽  
Time Resolved ◽  
Specific Manner ◽  
Context Specific

WNT/β-catenin signaling regulates gene expression across numerous biological contexts including development, stem cell homeostasis and tissue regeneration, and dysregulation of this pathway has been implicated in many diseases including cancer. One fundamental question is how distinct WNT target genes are activated in a context-specific manner, given the dogma that most, if not all, WNT/β-catenin responsive transcription is mediated by TCF/LEF transcription factors (TFs) that have similar DNA-binding specificities. Here we show that the SOX family of TFs direct lineage-specific WNT/β-catenin responsive transcription during the differentiation of human pluripotent stem cells (hPSCs) into definitive endoderm (DE) and neuromesodermal progenitors (NMPs). Using time-resolved multi-omics analyses, we show that β-catenin association with chromatin is highly dynamic, colocalizing with distinct TCFs and/or SOX TFs at distinct stages of differentiation, indicating both cooperative and competitive modes of genomic interactions. We demonstrate that SOX17 and SOX2 are required to recruit β-catenin to hundreds of lineage-specific WNT-responsive enhancers, many of which are not occupied by TCFs. At a subset of these TCF-independent enhancers, SOX TFs are required to both establish a permissive chromatin landscape and recruit a WNT-enhanceosome complex that includes β-catenin, BCL9, PYGO and transcriptional coactivators to direct SOX/β-catenin-dependent transcription. Given that SOX TFs are expressed in almost every cell type, these results have broad mechanistic implications for the specificity of WNT responses across many developmental and disease contexts.

scholarly journals ATF3 drives senescence by reconstructing accessible chromatin profiles

2020 ◽  
Author(s):  
Chao Zhang ◽  
Xuebin Zhang ◽  
Yiting Guan ◽  
Xiaoke Huang ◽  
Lijun Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factors ◽  
Regulatory Mechanism ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Dynamic Landscape ◽  
Intergenic Regions ◽  
Senescence Program ◽  
Accessible Chromatin

AbstractChromatin architecture and gene expression profile undergo tremendous reestablishment during senescence. However, the regulatory mechanism between chromatin reconstruction and gene expression in senescence remain elusive. The chromatin accessibility is an excellent perspective to reveal the latent regulatory elements. Thus, we depicted the landscapes of chromatin accessibility and gene expression during HUVECs senescence. We found that chromatin accessibilities are re-distributed during senescence. The senescence related increased accessible regions (IARs) and the decreased accessible regions (DARs) are mainly distributed in distal intergenic regions. The DARs are correlated with the function declines caused by senescence, whereas the IARs are involved in the regulation for senescence program. Moreover, the heterochromatin contributes most of IARs in senescent cells. We identified that the AP-1 transcription factors, especially ATF3 is responsible for driving chromatin accessibility reconstruction in IARs. In particular, DNA methylation is negatively correlated with chromatin accessibility during senescence. AP-1 motifs with low DNA methylation may improve their binding affinity in IARs and further opens the chromatin nearby. Our results described a dynamic landscape of chromatin accessibility whose remodeling contributes to the senescence program. And we identified a cellular senescence regulator, AP-1, which promotes senescence through organizing the accessibility profile in IARs.

Sign in / Sign up

Export Citation Format

Share Document