scholarly journals Comparative Chromatin Dynamics of Stem Cell Differentiation in Human and Rat

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.

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 ◽  
...  

2009 ◽  
Vol 27 (2) ◽  
pp. 93-102 ◽  
Author(s):  
Dorien A.M. van Dartel ◽  
Jeroen L.A. Pennings ◽  
Peter J.M. Hendriksen ◽  
Frederik J. van Schooten ◽  
Aldert H. Piersma

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

2021 ◽  
Author(s):  
Claire Barnes ◽  
David English ◽  
Megan Broderick ◽  
Mark Collins ◽  
Shaun M Cowley

Lysine specific demethylase 1 (LSD1) regulates gene expression as part of the CoREST complex, along with co-repressor of REST (CoREST) and histone deacetylase 1 (HDAC1). CoREST is recruited to specific...


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.


2020 ◽  
Author(s):  
Adi Alajem ◽  
Hava Roth ◽  
Sofia Ratgauzer ◽  
Danny Bavli ◽  
Alex Motzik ◽  
...  

AbstractIn mammals, cellular identity is defined through strict regulation of chromatin modifications and DNA methylation that control gene expression. Methylation of cytosines at CpG sites in the genome is mainly associated with suppression; however, the reason for enhancer-specific methylation is not fully understood. We used sequential ChIP-bisulfite-sequencing for H3K4me1 and H3K27ac histone marks. By collecting data from the same genomic region, we identified enhancers differentially methylated between these two marks. We observed a global gain of CpG methylation primarily in H3K4me1-marked nucleosomes during mouse embryonic stem cell differentiation. This gain occurred largely in enhancer regions that regulate genes critical for differentiation. The higher levels of DNA methylation in H3K4me1-versus H3K27ac-marked enhancers, despite it being the same genomic region, indicates cellular heterogeneity of enhancer states. Analysis of single-cell RNA-seq profiles demonstrated that this heterogeneity correlates with gene expression during differentiation. Furthermore, heterogeneity of enhancer methylation correlates with transcription start site methylation. Our results provide insights into enhancer-based functional variation in complex biological systems.Author summaryCellular dynamics are underlined by numerous regulatory layers. The regulatory mechanism of interest in this work are enhancers. Enhancers are regulatory regions responsible, mainly, for increasing the possibility of transcription of a certain gene. Enhancers are marked by two distinct chemical groups-H3K4me1 and H3K27ac on the tail of histones. Histones are the proteins responsible for DNA packaging into condensed chromatin structure. In contrast, DNA methylation is a chemical modification often found on enhancers, and is traditionally associated with repression. A long debated question revolves around the functional relevance of DNA methylation in the context of enhancers. Here, we combined the two regulatory layers, histone marks and DNA methylation, to a single measurement that can highlight DNA methylation separately on each histone mark but at the same genomic region. When isolated with H3K4me1, enhancers showed higher levels of methylation compared to H3K27ac. As we measured the same genomic locations, we show that differences of DNA methylation between these marks can only be explained by cellular heterogeneity. We also demonstrated that these enhancers tend to play roles in stem cell differentiation and expression levels of the genes they control correlate with cell-to-cell variation.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Gabriel N Aughey ◽  
Alicia Estacio Gomez ◽  
Jamie Thomson ◽  
Hang Yin ◽  
Tony D Southall

During development eukaryotic gene expression is coordinated by dynamic changes in chromatin structure. Measurements of accessible chromatin are used extensively to identify genomic regulatory elements. Whilst chromatin landscapes of pluripotent stem cells are well characterised, chromatin accessibility changes in the development of somatic lineages are not well defined. Here we show that cell-specific chromatin accessibility data can be produced via ectopic expression of E. coli Dam methylase in vivo, without the requirement for cell-sorting (CATaDa). We have profiled chromatin accessibility in individual cell-types of Drosophila neural and midgut lineages. Functional cell-type-specific enhancers were identified, as well as novel motifs enriched at different stages of development. Finally, we show global changes in the accessibility of chromatin between stem-cells and their differentiated progeny. Our results demonstrate the dynamic nature of chromatin accessibility in somatic tissues during stem cell differentiation and provide a novel approach to understanding gene regulatory mechanisms underlying development.


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