scholarly journals The chromatin-regulating CoREST complex is animal specific and essential for development in the cnidarian Nematostella vectensis

2021 ◽  
Author(s):  
James M Gahan ◽  
Maria Hernandez-Valladares ◽  
Fabian Rentzsch

Chromatin-modifying proteins are key players in the regulation of development and cell differentiation in animals. Many individual chromatin modifiers, however, predate the evolution of animal multicellularity and how they became integrated into the regulatory networks underlying development is unclear. Here we show that CoREST is an animal-specific protein that assembles a conserved, vertebrate-like histone-modifying complex including Lsd1 and HDAC1/2 in the sea anemone Nematostella vectensis. We further show that NvCoREST expression overlaps fully with that of NvLsd1 throughout development. NvCoREST mutants, generated using CRISPR-Cas9, reveal essential roles during development and for the differentiation of cnidocytes, thereby phenocopying NvLsd1 mutants. We also show that this requirement is cell autonomous using a cell-type-specific rescue approach. Together, this shows that the evolution of CoREST allowed the formation of a chromatin-modifying complex that was present before the last common cnidarian-bilaterian ancestor and thus represents an ancient component of the animal developmental toolkit.

2011 ◽  
Vol 21 (6) ◽  
pp. 1391-1401 ◽  
Author(s):  
C. Kohama ◽  
H. Kato ◽  
K. Numata ◽  
M. Hirose ◽  
T. Takemasa ◽  
...  

2020 ◽  
Author(s):  
Alireza Fotuhi Siahpirani ◽  
Deborah Chasman ◽  
Morten Seirup ◽  
Sara Knaack ◽  
Rupa Sridharan ◽  
...  

AbstractChanges in transcriptional regulatory networks can significantly alter cell fate. To gain insight into transcriptional dynamics, several studies have profiled transcriptomes and epigenomes at different stages of a developmental process. However, integrating these data across multiple cell types to infer cell type specific regulatory networks is a major challenge because of the small sample size for each time point. We present a novel approach, Dynamic Regulatory Module Networks (DRMNs), to model regulatory network dynamics on a cell lineage. DRMNs represent a cell type specific network by a set of expression modules and associated regulatory programs, and probabilistically model the transitions between cell types. DRMNs learn a cell type’s regulatory network from input expression and epigenomic profiles using multi-task learning to exploit cell type relatedness. We applied DRMNs to study regulatory network dynamics in two different developmental dynamic processes including cellular reprogramming and liver dedifferentiation. For both systems, DRMN predicted relevant regulators driving the major patterns of expression in each time point as well as regulators for transitioning gene sets that change their expression over time.


2021 ◽  
Author(s):  
Taylor M. Lagler ◽  
Yuchen Yang ◽  
Yuriko Harigaya ◽  
Vijay G. Sankaran ◽  
Ming Hu ◽  
...  

Existing studies of chromatin conformation have primarily focused on potential enhancers interacting with gene promoters. By contrast, the interactivity of promoters per se, while equally critical to understanding transcriptional control, has been largely unexplored, particularly in a cell type-specific manner for blood lineage cell types. In this study, we leverage promoter capture Hi-C data across a compendium of blood lineage cell types to identify and characterize cell type-specific super-interactive promoters (SIPs). Notably, promoter-interacting regions (PIRs) of SIPs are more likely to overlap with cell type-specific ATAC-seq peaks and GWAS variants for relevant blood cell traits than PIRs of non-SIPs. Further, SIP genes tend to express at a higher level in the corresponding cell type, and show enriched heritability of relevant blood cell trait(s). Importantly, this analysis shows the potential of using promoter-centric analyses of chromatin spatial organization data to identify biologically important genes and their regulatory regions.


2010 ◽  
Vol 39 (3) ◽  
pp. 455-467 ◽  
Author(s):  
Kasia G. Gora ◽  
Christos G. Tsokos ◽  
Y. Erin Chen ◽  
Balaji S. Srinivasan ◽  
Barrett S. Perchuk ◽  
...  

2020 ◽  
Author(s):  
Pawan K. Jha ◽  
Utham K. Valekunja ◽  
Sandipan Ray ◽  
Mathieu Nollet ◽  
Akhilesh B. Reddy

Every day, we sleep for a third of the day. Sleep is important for cognition, brain waste clearance, metabolism, and immune responses. The molecular mechanisms governing sleep are largely unknown. Here, we used a combination of single cell RNA sequencing and cell-type specific proteomics to interrogate the molecular underpinnings of sleep. Different cell types in three important brain regions for sleep (brainstem, cortex, and hypothalamus) exhibited diverse transcriptional responses to sleep need. Sleep restriction modulates astrocyte-neuron crosstalk and sleep need enhances expression of specific sets of transcription factors in different brain regions. In cortex, we also interrogated the proteome of two major cell types: astrocytes and neurons. Sleep deprivation differentially alters the expression of proteins in astrocytes and neurons. Similarly, phosphoproteomics revealed large shifts in cell-type specific protein phosphorylation. Our results indicate that sleep need regulates transcriptional, translational, and post-translational responses in a cell-specific manner.


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