scholarly journals Dot1L interaction partner AF10 safeguards cell identity during the acquisition of pluripotency

2020 ◽  
Author(s):  
Coral K. Wille ◽  
Edwin N. Neumann ◽  
Aniruddha J. Deshpande ◽  
Rupa Sridharan

ABSTRACTHistone-modifying enzymes function as part of protein complexes that alter the accessibility of chromatin to elicit differential gene expression patterns. Dot1L, the sole histone H3 lysine (K) 79 (H3K79) methyltransferase, is associated with proteins that recognize specific histone modifications and target Dot1L to particular chromatin contexts. Here we find that depletion of the Dot1L interacting protein AF10, which recognizes unmodified H3K27, mimics Dot1L catalytic inhibition to increase the efficiency of reprogramming somatic cells to induced pluripotent stem cells (iPSCs). AF10 deletion results in almost no steady state transcriptional changes yet is responsible for half of the Dot1L iPSC reprogramming phenotype. In contrast, reduced levels of Dot1L interactors AF9 and ENL that recognize H3 acetylation decrease iPSC generation. Despite the opposite effects in reprogramming of Dot1L interacting proteins with differing histone reader specificity, we find that the AF10-histone interaction domain is dispensable for increased iPSC generation. Instead, the AF10-Dot1L interaction domain that potentiates H3K79 di- and tri-methylation is a barrier to pluripotency acquisition. Taken together we reveal a key role for higher order gene body histone methylation in safeguarding cell identity.

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wei Wang ◽  
Lei Wang ◽  
Ling Wang ◽  
Meilian Tan ◽  
Collins O. Ogutu ◽  
...  

Abstract Background Oil flax (linseed, Linum usitatissimum L.) is one of the most important oil crops., However, the increases in drought resulting from climate change have dramatically reduces linseed yield and quality, but very little is known about how linseed coordinates the expression of drought resistance gene in response to different level of drought stress (DS) on the genome-wide level. Results To explore the linseed transcriptional response of DS and repeated drought (RD) stress, we determined the drought tolerance of different linseed varieties. Then we performed full-length transcriptome sequencing of drought-resistant variety (Z141) and drought-sensitive variety (NY-17) under DS and RD stress at the seedling stage using single-molecule real-time sequencing and RNA-sequencing. Gene Ontology (GO) and reduce and visualize GO (REVIGO) enrichment analysis showed that upregulated genes of Z141 were enriched in more functional pathways related to plant drought tolerance than those of NY-17 were under DS. In addition, 4436 linseed transcription factors were identified, and 1190 were responsive to stress treatments. Moreover, protein-protein interaction (PPI) network analysis showed that the proline biosynthesis pathway interacts with stress response genes through RAD50 (DNA repair protein 50) interacting protein 1 (RIN-1). Finally, proline biosynthesis and DNA repair structural gene expression patterns were verified by RT- PCR. Conclusions The drought tolerance of Z141 may be related to its upregulation of drought tolerance genes under DS. Proline may play an important role in linseed drought tolerance by maintaining cell osmotic and protecting DNA from ROS damage. In summary, this study provides a new perspective to understand the drought adaptability of linseed.


2021 ◽  
Vol 22 (9) ◽  
pp. 4634
Author(s):  
Wenxuan Du ◽  
Junfeng Yang ◽  
Lin Ma ◽  
Qian Su ◽  
Yongzhen Pang

The calcineurin B-like protein (CBL) and CBL-interacting protein kinase (CIPK) play important roles in plant signal transduction and response to abiotic stress. Plants of Medicago genus contain many important forages, and their growth is often affected by a variety of abiotic stresses. However, studies on the CBL and CIPK family member and their function are rare in Medicago. In this study, a total of 23 CBL and 58 CIPK genes were identified from the genome of Medicago sativa as an important forage crop, and Medicaog truncatula as the model plant. Phylogenetic analysis suggested that these CBL and CIPK genes could be classified into five and seven groups, respectively. Moreover, these genes/proteins showed diverse exon-intron organizations, architectures of conserved protein motifs. Many stress-related cis-acting elements were found in their promoter region. In addition, transcriptional analyses showed that these CBL and CIPK genes exhibited distinct expression patterns in various tissues, and in response to drought, salt, and abscisic acid treatments. In particular, the expression levels of MtCIPK2 (MsCIPK3), MtCIPK17 (MsCIPK11), and MtCIPK18 (MsCIPK12) were significantly increased under PEG, NaCl, and ABA treatments. Collectively, our study suggested that CBL and CIPK genes play crucial roles in response to various abiotic stresses in Medicago.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shaona Acharjee ◽  
Paul M. K. Gordon ◽  
Benjamin H. Lee ◽  
Justin Read ◽  
Matthew L. Workentine ◽  
...  

AbstractMicroglia play an important role in the pathogenesis of multiple sclerosis and the mouse model of MS, experimental autoimmune encephalomyelitis (EAE). To more fully understand the role of microglia in EAE we characterized microglial transcriptomes before the onset of motor symptoms (pre-onset) and during symptomatic EAE. We compared the transcriptome in brain, where behavioral changes are initiated, and spinal cord, where damage is revealed as motor and sensory deficits. We used a RiboTag strategy to characterize ribosome-bound mRNA only in microglia without incurring possible transcriptional changes after cell isolation. Brain and spinal cord samples clustered separately at both stages of EAE, indicating regional heterogeneity. Differences in gene expression were observed in the brain and spinal cord of pre-onset and symptomatic animals with most profound effects in the spinal cord of symptomatic animals. Canonical pathway analysis revealed changes in neuroinflammatory pathways, immune functions and enhanced cell division in both pre-onset and symptomatic brain and spinal cord. We also observed a continuum of many pathways at pre-onset stage that continue into the symptomatic stage of EAE. Our results provide additional evidence of regional and temporal heterogeneity in microglial gene expression patterns that may help in understanding mechanisms underlying various symptomology in MS.


Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 82
Author(s):  
Yunxiao Wei ◽  
Guoliang Li ◽  
Shujiang Zhang ◽  
Shifan Zhang ◽  
Hui Zhang ◽  
...  

Allopolyploidy is an evolutionary and mechanistically intriguing process involving the reconciliation of two or more sets of diverged genomes and regulatory interactions, resulting in new phenotypes. In this study, we explored the gene expression patterns of eight F2 synthetic Brassica napus using RNA sequencing. We found that B. napus allopolyploid formation was accompanied by extensive changes in gene expression. A comparison between F2 and the parent shows a certain proportion of differentially expressed genes (DEG) and activation\silent gene, and the two genomes (female parent (AA)\male parent (CC) genomes) showed significant differences in response to whole-genome duplication (WGD); non-additively expressed genes represented a small portion, while Gene Ontology (GO) enrichment analysis showed that it played an important role in responding to WGD. Besides, genome-wide expression level dominance (ELD) was biased toward the AA genome, and the parental expression pattern of most genes showed a high degree of conservation. Moreover, gene expression showed differences among eight individuals and was consistent with the results of a cluster analysis of traits. Furthermore, the differential expression of waxy synthetic pathways and flowering pathway genes could explain the performance of traits. Collectively, gene expression of the newly formed allopolyploid changed dramatically, and this was different among the selfing offspring, which could be a prominent cause of the trait separation. Our data provide novel insights into the relationship between the expression of differentially expressed genes and trait segregation and provide clues into the evolution of allopolyploids.


Genetics ◽  
1998 ◽  
Vol 148 (4) ◽  
pp. 1865-1874
Author(s):  
Christina Rosen ◽  
Dale Dorsett ◽  
Joseph Jack

Abstract The DNA-binding protein encoded by the zeste gene of Drosophila activates transcription and mediates interchromosomal interactions such as transvection. The mutant protein encoded by the zeste1 (z1) allele retains the ability to support transvection, but represses white. Similar to transvection, repression requires Zeste-Zeste protein interactions and a second copy of white, either on the homologous chromosome or adjacent on the same chromosome. We characterized two pseudorevertants of z1 (z1-35 and z1-42) and another zeste mutation (z78c) that represses white. The z1 lesion alters a lysine residue located between the N-terminal DNA-binding domain and the C-terminal hydrophobic repeats involved in Zeste self-interactions. The z78c mutation alters a histidine near the site of the z1 lesion. Both z1 pseudorevertants retain the z1 lesion and alter different prolines in a proline-rich region located between the z1 lesion and the self-interaction domain. The pseudorevertants retain the ability to self-interact, but fail to repress white or support transvection at Ultrabithorax. To account for these observations and evidence indicating that Zeste affects gene expression through Polycomb group (Pc-G) protein complexes that epigenetically maintain chromatin states, we suggest that the regions affected by the z1, z78c, and pseudorevertant lesions mediate interactions between Zeste and the maintenance complexes.


2004 ◽  
Vol 20 (17) ◽  
pp. 3146-3155 ◽  
Author(s):  
Y. Lai ◽  
B. Wu ◽  
L. Chen ◽  
H. Zhao

2021 ◽  
Vol 12 ◽  
Author(s):  
Hongjiang Liu ◽  
Yundong Zou ◽  
Chen Chen ◽  
Yundi Tang ◽  
Jianping Guo

Systemic lupus erythematosus (SLE) is a common and potentially fatal autoimmune disease that affects multiple organs. To date, its etiology and pathogenesis remains elusive. Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs with covalently closed loop structure. Growing evidence has demonstrated that circRNAs may play an essential role in regulation of gene expression and transcription by acting as microRNA (miRNA) sponges, impacting cell survival and proliferation by interacting with RNA binding proteins (RBPs), and strengthening mRNA stability by forming RNA-protein complexes duplex structures. The expression patterns of circRNAs exhibit tissue-specific and pathogenesis-related manner. CircRNAs have implicated in the development of multiple autoimmune diseases, including SLE. In this review, we summarize the characteristics, biogenesis, and potential functions of circRNAs, its impact on immune responses and highlight current understanding of circRNAs in the pathogenesis of SLE.


2021 ◽  
Author(s):  
Devon Birdseye ◽  
Laura A. de Boer ◽  
Hua Bai ◽  
Peng Zhou ◽  
Zhouxin Shen ◽  
...  

AbstractThe use of hybrids is widespread in agriculture, yet the molecular basis for hybrid vigor (heterosis) remains obscure. To identify molecular components that may contribute to the known higher photosynthetic capacity of maize hybrids, we generated paired datasets of the proteomes and transcriptomes from leaf tissues of maize hybrids and their inbred parents. Expression patterns in the hybrids were semi-dominant to overdominant for subunits of the digenomic protein complexes required for the light reactions of photosynthesis and for chloroplast protein synthesis; nuclear and plastid-encoded subunits were elevated similarly. These patterns were not mirrored in the nuclear transcriptomes. We compared growth to transcript and protein levels of multiple hybrids with varying levels of heterosis. Expression heterosis (hybrid/mid-parent expression levels) of chloroplast ribosomal proteins and of nuclear transcripts for the photosynthetic light reactions was positively correlated with plant height heterosis (hybrid/mid-parent plant height). Ethylene biosynthetic enzymes were expressed below mid-parent levels in the hybrids, and the ethylene biosynthesis mutant acs2/acs6 partially phenocopied the hybrid proteome, indicating that a reduction in ethylene biosynthesis may be upstream of the elevated expression of photosynthetic and ribosomal proteins in chloroplasts of hybrids.


2018 ◽  
Author(s):  
Jason Lee ◽  
Miguel Ochoa ◽  
Pablo Maceda ◽  
Eun Yoon ◽  
Lara Samarneh ◽  
...  

Transgenic methods for direct reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) are effective in cell culture systems but ultimately limit the utility of iPSCs due to concerns of mutagenesis and tumor formation. Recent studies have suggested that some transgenes can be eliminated by using small molecules as an alternative to transgenic methods of iPSC generation. We developed a high throughput platform for applying complex dynamic mechanical forces to cultured cells. Using this system, we screened for optimized conditions to stimulate the activation of Oct-4 and other transcription factors to prime the development of pluripotency in mouse fibroblasts. Using high throughput mechanobiological screening assays, we identified small molecules that can synergistically enhance the priming of pluripotency of mouse fibroblasts in combination with mechanical loading. Taken together, our findings demonstrate the ability of mechanical forces to induce reprograming factors and support that biophysical conditioning can act cooperatively with small molecules to priming the induction pluripotency in somatic cells.


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