scholarly journals Multi-omic profiling of histone variant H3.3 lysine 27 methylation reveals a distinct role from canonical H3 in stem cell differentiation

2022 ◽  
Author(s):  
Yekaterina Kori ◽  
Peder J. Lund ◽  
Matteo Trovato ◽  
Simone Sidoli ◽  
Zuofei Yuan ◽  
...  

Histone variants, such as histone H3.3, replace canonical histones within the nucleosome to alter chromatin accessibility and gene expression. Although the biological roles of selected histone post-translational modifications (PTMs) have...

2020 ◽  
Author(s):  
Giancarlo Bonora ◽  
Vijay Ramani ◽  
Ritambhara Singh ◽  
He Fang ◽  
Dana Jackson ◽  
...  

AbstractMammalian development is associated with extensive changes in gene expression, chromatin accessibility, and nuclear structure. Here, we follow such changes associated with mouse embryonic stem cell differentiation and X inactivation by integrating, for the first time, allele-specific data obtained by high-throughput single-cell RNA-seq, ATAC-seq, and Hi-C. In differentiated cells, contact decay profiles, which clearly distinguish the active and inactive X chromosomes, reveal loss of the inactive X-specific structure at mitosis followed by a rapid reappearance, suggesting a ‘bookkeeping’ mechanism. In differentiating embryonic stem cells, changes in contact decay profiles are detected in parallel on both the X chromosomes and autosomes, suggesting profound simultaneous reorganization. The onset of the inactive X-specific structure in single cells is notably delayed relative to that of gene silencing, consistent with the idea that chromatin compaction is a late event of X inactivation. Novel computational approaches to effectively align single-cell gene expression, chromatin accessibility, and 3D chromosome structure reveal that long-range structural changes to chromosomes appear as discrete events, unlike progressive changes in gene expression and chromatin accessibility.


2021 ◽  
Author(s):  
Christina Wilcox Thai ◽  
Shan Jiang ◽  
Yuka Roxas ◽  
Cassandra McGill ◽  
Savanna Ma ◽  
...  

ABSTRACTDifferentiation of cell types homologous between species are controlled by conserved networks of regulatory elements driving gene expression. In order to identify conservation of gene expression and chromatin accessibility during cell differentiation in two different species. We collected a daily time-course of gene expression and chromatin accessibility in rat and human to quantify conserved and species-specific chromatin dynamics during embryonic stem cell differentiation to definitive endoderm (DE) as well as to neuronal progenitor cells (NPC). We identify shared and cell-type specific transient differentiation markers in each species, including key transcription factors that may regulate differentiation into each cell-type and their candidate cis-regulatory elements (cCREs). Our analysis shows that DE differentiation has higher conservation of gene expression and chromatin accessibility than NPC differentiation. We provide the first global comparison of transcriptional complexity and chromatin dynamics between human and rat for DE and NPC differentiation.


2021 ◽  
Author(s):  
Yekaterina Kori ◽  
Peder J. Lund ◽  
Matteo Trovato ◽  
Simone Sidoli ◽  
Zuo-Fei Yuan ◽  
...  

Histone variants, such as histone H3.3, replace canonical histones within the nucleosome to alter chromatin accessibility and gene expression. Although the biological roles of selected histone post-translational modifications (PTMs) have been extensively characterized, the potential differences in the function of a given PTM on different histone variants is almost always elusive. By applying proteomics and genomics techniques, we investigate the role of lysine 27 tri-methylation specifically on the histone variant H3.3 (H3.3K27me3) in the context of mouse embryonic stem cell pluripotency and differentiation as a model system for development. We demonstrate that while the steady state overall levels of methylation on both H3K27 and H3.3K27 decrease during differentiation, methylation dynamics studies indicate that methylation on H3.3K27 is maintained more than on H3K27. Using a custom-made antibody, we identify a unique enrichment of H3.3K27me3 at lineage-specific genes, such as olfactory receptor genes, and at binding motifs for the transcription factors FOXJ2/3. REST, a predicted FOXJ2/3 target that acts as a transcriptional repressor of terminal neuronal genes, was identified with H3.3K27me3 at its promoter region. H3.3K27A mutant cells confirmed an upregulation of FOXJ2/3 targets upon the loss of methylation at H3.3K27. Thus, while canonical H3K27me3 has been characterized to regulate the expression of transcription factors that play a general role in differentiation, our work suggests H3.3K27me3 is essential for regulating distinct terminal differentiation genes. This work highlights the importance of understanding the effects of PTMs not only on canonical histones but also on specific histone variants, as they may exhibit distinct roles.


2011 ◽  
Vol 251 (2) ◽  
pp. 110-118 ◽  
Author(s):  
Dorien A.M. van Dartel ◽  
Jeroen L.A. Pennings ◽  
Liset J.J. de la Fonteyne ◽  
Karen J.J. Brauers ◽  
Sandra Claessen ◽  
...  

2010 ◽  
Vol 119 (1) ◽  
pp. 126-134 ◽  
Author(s):  
Dorien A. M. van Dartel ◽  
Jeroen L. A. Pennings ◽  
Liset J. J. de la Fonteyne ◽  
Karen J. J. Brauers ◽  
Sandra Claessen ◽  
...  

2014 ◽  
Vol 28 (4) ◽  
pp. 351-365 ◽  
Author(s):  
Mélanie A. Eckersley-Maslin ◽  
David Thybert ◽  
Jan H. Bergmann ◽  
John C. Marioni ◽  
Paul Flicek ◽  
...  

2005 ◽  
Vol 14 (6) ◽  
pp. 608-620 ◽  
Author(s):  
Roman M. Salasznyk ◽  
Robert F. Klees ◽  
Aaron M. Westcott ◽  
Scott Vandenberg ◽  
Kristin Bennett ◽  
...  

Physiology ◽  
2018 ◽  
Vol 33 (1) ◽  
pp. 16-25 ◽  
Author(s):  
Lucas R. Smith ◽  
Sangkyun Cho ◽  
Dennis E. Discher

Stem cells mechanosense the stiffness of their microenvironment, which impacts differentiation. Although tissue hydration anti-correlates with stiffness, extracellular matrix (ECM) stiffness is clearly transduced into gene expression via adhesion and cytoskeleton proteins that tune fates. Cytoskeletal reorganization of ECM can create heterogeneity and influence fates, with fibrosis being one extreme.


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