scholarly journals CFP-1 interacts with HDAC1/2 complexes inC. elegansdevelopment

2018 ◽  
Author(s):  
Bharat Pokhrel ◽  
Yannic Chen ◽  
Jonathan Joseph Biro
Keyword(s):  
Cell Fate ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Dependent Manner ◽  
Cell Fate Specification ◽  
C Elegans ◽  
Evolutionarily Conserved ◽  
Epigenetic Regulator ◽  
Inducible Genes

AbstractCFP-1 (CXXC finger binding protein 1) is an evolutionarily conserved protein that binds to non-methylated CpG-rich promoters in humans andC. elegans. This conserved epigenetic regulator is a part of the COMPASS complex that contains the H3K4me3 methyltransferase SET1 in mammals and SET-2 inC. elegans. Previous studies have indicated the importance ofcfp-1in embryonic stem cell differentiation and cell fate specification. However, neither the function nor the mechanism of action ofcfp-1is well understood at the organismal level. To further investigate the function of CFP-1, we have characterisedC. elegansCOMPASS mutantscfp-1(tm6369)andset-2(bn129). We found that bothcfp-1andset-2play an important role in the regulation of fertility and development of the organism. Furthermore, we found that bothcfp-1andset-2are required for H3K4 trimethylation and play a repressive role in the expression of heat shock and salt-inducible genes. Interestingly, we found thatcfp-1but notset-2genetically interacts with Histone Deacetylase (HDAC1/2) complexes to regulate fertility, suggesting a function of CFP-1 outside of the COMPASS complex. Additionally we found thatcfp-1andset-2acts on a separate pathways to regulate fertility and development ofC. elegans. Our results suggest that CFP-1 genetically interacts with HDAC1/2 complexes to regulate fertility, independent of its function within COMPASS complex. We propose that CFP-1 could cooperate with COMPASS complex and/or HDAC1/2 in a context dependent manner.

scholarly journals miRNAs in ESC differentiation

2012 ◽  
Vol 303 (8) ◽  
pp. H931-H939 ◽  
Author(s):  
Emanuele Berardi ◽  
Matthias Pues ◽  
Lieven Thorrez ◽  
Maurilio Sampaolesi
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Critical Role ◽  
Embryonic Stem ◽  
Noncoding Rnas ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Mammalian Development ◽  
Small Noncoding Rnas ◽  
Rna Duplexes

MicroRNAs (miRNAs) are small sequences of noncoding RNAs that regulate gene expression by two basic processes: direct degradation of mRNA and translation inhibition. miRNAs are key molecules in gene regulation for embryonic stem cells, since they are able to repress target pluripotent mRNA genes, including Oct4, Sox2, and Nanog. miRNAs are unlike other small noncoding RNAs in their biogenesis, since they derive from precursors that fold back to form a distinctive hairpin structure, whereas other classes of small RNAs are formed from longer hairpins or bimolecular RNA duplexes (siRNAs) or precursors without double-stranded character (piRNAs). An increasing amount of evidence suggests that miRNAs may have a critical role in the maintenance of the pluripotent cell state and in the regulation of early mammalian development. This review gives an overview of the current state of the art of miRNA expression and regulation in embryonic stem cell differentiation. Current insights on controlling stem cell fate toward mesodermal, endodermal and ectodermal differentiation, and cell reprogramming are also highlighted.

scholarly journals OLIG2 regulates lncRNAs and its own expression during oligodendrocyte lineage formation

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Haichao Wei ◽  
Xiaomin Dong ◽  
Yanan You ◽  
Bo Hai ◽  
Raquel Cuevas-Diaz Duran ◽  
...  
Keyword(s):  
Cell Fate ◽  
Epigenetic Modification ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Transcriptional Level ◽  
Oligodendrocyte Progenitor Cells ◽  
Cell Fate Decisions ◽  
Oligodendrocyte Development

Abstract Background Oligodendrocytes, responsible for axon ensheathment, are critical for central nervous system (CNS) development, function, and diseases. OLIG2 is an important transcription factor (TF) that acts during oligodendrocyte development and performs distinct functions at different stages. Previous studies have shown that lncRNAs (long non-coding RNAs; > 200 bp) have important functions during oligodendrocyte development, but their roles have not been systematically characterized and their regulation is not yet clear. Results We performed an integrated study of genome-wide OLIG2 binding and the epigenetic modification status of both coding and non-coding genes during three stages of oligodendrocyte differentiation in vivo: neural stem cells (NSCs), oligodendrocyte progenitor cells (OPCs), and newly formed oligodendrocytes (NFOs). We found that 613 lncRNAs have OLIG2 binding sites and are expressed in at least one cell type, which can potentially be activated or repressed by OLIG2. Forty-eight of them have increased expression in oligodendrocyte lineage cells. Predicting lncRNA functions by using a “guilt-by-association” approach revealed that the functions of these 48 lncRNAs were enriched in “oligodendrocyte development and differentiation.” Additionally, bivalent genes are known to play essential roles during embryonic stem cell differentiation. We identified bivalent genes in NSCs, OPCs, and NFOs and found that some bivalent genes bound by OLIG2 are dynamically regulated during oligodendrocyte development. Importantly, we unveiled a previously unknown mechanism that, in addition to transcriptional regulation via DNA binding, OLIG2 could self-regulate through the 3′ UTR of its own mRNA. Conclusions Our studies have revealed the missing links in the mechanisms regulating oligodendrocyte development at the transcriptional level and after transcription. The results of our research have improved the understanding of fundamental cell fate decisions during oligodendrocyte lineage formation, which can enable insights into demyelination diseases and regenerative medicine.

scholarly journals Cleavage of histone H2A during embryonic stem cell differentiation destabilizes nucleosomes to counteract gene activation

2021 ◽  
Author(s):  
Mariel Coradin ◽  
Joseph Cesare ◽  
Yemin Lan ◽  
Zhexin Zhu ◽  
Peder J. Lund ◽  
...  
Keyword(s):  
Cell Fate ◽  
Es Cells ◽  
Expression Patterns ◽  
Gene Activation ◽  
Embryonic Stem ◽  
Maximum Level ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Cell Fate Decisions ◽  
Lysosomal Protease

Histone proteolysis is a poorly understood phenomenon in which the N-terminal tails of histones are irreversibly cleaved by intracellular proteases. During development, histone post-translational modifications are known to orchestrate gene expression patterns that ultimately drive cell fate decisions. Therefore, deciphering the mechanisms of histone proteolysis is necessary to enhance the understanding of cellular differentiation. Here we show that H2A is cleaved by the lysosomal protease Cathepsin L during ESCs differentiation. Using quantitative mass spectrometry (MS), we identified L23 to be the primary cleavage site that gives rise to the clipped form of H2A (cH2A), which reaches a maximum level of ~1% of total H2A after four days of differentiation. Using ChIP-seq, we found that preventing proteolysis leads to an increase in acetylated H2A at promoter regions in differentiated ES cells. We also report the identification of novel readers of acetylated H2A in pluripotent ES cells, including members of the PBAF remodeling complex, which can recognize different acetylated forms of H2A. Finally, we show that H2A proteolysis abolishes this recognition. Altogether, our data suggests that proteolysis serves as an efficient mechanism to silence pluripotency genes and destabilize the nucleosome core particle.

scholarly journals Oxygen Regulation in Development: Lessons from Embryogenesis towards Tissue Engineering

2018 ◽  
Vol 205 (5-6) ◽  
pp. 350-371 ◽  
Author(s):  
Shahrzad Fathollahipour ◽  
Pritam S. Patil ◽  
Nic D. Leipzig
Keyword(s):  
Tissue Engineering ◽  
Stem Cell ◽  
Cell Fate ◽  
Adult Development ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Low Oxygen ◽  
Oxygen Levels ◽  
Oxygen Tensions

Oxygen is a vital source of energy necessary to sustain and complete embryonic development. Not only is oxygen the driving force for many cellular functions and metabolism, but it is also involved in regulating stem cell fate, morphogenesis, and organogenesis. Low oxygen levels are the naturally preferred microenvironment for most processes during early development and mainly drive proliferation. Later on, more oxygen and also nutrients are needed for organogenesis and morphogenesis. Therefore, it is critical to maintain oxygen levels within a narrow range as required during development. Modulating oxygen tensions is performed via oxygen homeostasis mainly through the function of hypoxia-inducible factors. Through the function of these factors, oxygen levels are sensed and regulated in different tissues, starting from their embryonic state to adult development. To be able to mimic this process in a tissue engineering setting, it is important to understand the role and levels of oxygen in each developmental stage, from embryonic stem cell differentiation to organogenesis and morphogenesis. Taking lessons from native tissue microenvironments, researchers have explored approaches to control oxygen tensions such as hemoglobin-based, perfluorocarbon-based, and oxygen-generating biomaterials, within synthetic tissue engineering scaffolds and organoids, with the aim of overcoming insufficient or nonuniform oxygen levels and nutrient supply.

scholarly journals Evolutionarily Conserved Transcriptional Co-Expression Guiding Embryonic Stem Cell Differentiation

PLoS ONE ◽  
2008 ◽  
Vol 3 (10) ◽  
pp. e3406 ◽  
Author(s):  
Yu Sun ◽  
Huai Li ◽  
Ying Liu ◽  
Mark P. Mattson ◽  
Mahendra S. Rao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Evolutionarily Conserved
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