Promoter-enhancer looping and shadow enhancers of the mouse αA-crystallin locus

McGreal-Estrada, Rebecca S.; Wolf, Louise; Cvekl, Aleš

doi:10.1242/bio.036897

Cited by 7 publications

(4 citation statements)

References 46 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9 A). A weaker ATAC-seq signal further upstream corresponds to evolutionary conserved enhancer region [ 80 ]. As expected, histone H3.3 is more abundant at the Cryaa gene in P0.5 lens fibers compared to the epithelium (Fig.…”

Section: Resultsmentioning

confidence: 99%

Dynamic changes in whole genome DNA methylation, chromatin and gene expression during mouse lens differentiation

Chang

Zhao

Rayêe

et al. 2023

Epigenetics & Chromatin

Self Cite

View full text Add to dashboard Cite

Background Cellular differentiation is marked by temporally and spatially coordinated gene expression regulated at multiple levels. DNA methylation represents a universal mechanism to control chromatin organization and its accessibility. Cytosine methylation of CpG dinucleotides regulates binding of methylation-sensitive DNA-binding transcription factors within regulatory regions of transcription, including promoters and distal enhancers. Ocular lens differentiation represents an advantageous model system to examine these processes as lens comprises only two cell types, the proliferating lens epithelium and postmitotic lens fiber cells all originating from the epithelium. Results Using whole genome bisulfite sequencing (WGBS) and microdissected lenses, we investigated dynamics of DNA methylation and chromatin changes during mouse lens fiber and epithelium differentiation between embryos (E14.5) and newborns (P0.5). Histone H3.3 variant chromatin landscapes were also generated for both P0.5 lens epithelium and fibers by chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq). Tissue-specific features of DNA methylation patterns are demonstrated via comparative studies with embryonic stem (ES) cells and neural progenitor cells (NPCs) at Nanog, Pou5f1, Sox2, Pax6 and Six3 loci. Comparisons with ATAC-seq and RNA-seq data demonstrate that reduced methylation is associated with increased expression of fiber cell abundant genes, including crystallins, intermediate filament (Bfsp1 and Bfsp2) and gap junction proteins (Gja3 and Gja8), marked by high levels of histone H3.3 within their transcribed regions. Interestingly, Pax6-binding sites exhibited predominantly DNA hypomethylation in lens chromatin. In vitro binding of Pax6 proteins showed Pax6’s ability to interact with sites containing one or two methylated CpG dinucleotides. Conclusions Our study has generated the first data on methylation changes between two different stages of mammalian lens development and linked these data with chromatin accessibility maps, presence of histone H3.3 and gene expression. Reduced DNA methylation correlates with expression of important genes involved in lens morphogenesis and lens fiber cell differentiation.

show abstract

Section: Resultsmentioning

confidence: 99%

Dynamic changes in whole genome DNA methylation, chromatin and gene expression during mouse lens differentiation

Chang

Zhao

Rayêe

et al. 2023

Epigenetics & Chromatin

Self Cite

View full text Add to dashboard Cite

show abstract

“…Hi-C examines the 3D structure of DNA and chromatin by ligating DNA loci that are spatially proximate to one another and is followed by their sequencing reaching resolution between 1 and 10 kb [ 215 ]. In the lens, promoter-enhancer looping has only examined between 5′- and 3′-located distal enhancers of the mouse αA-crystallin ( Cryaa ) locus [ 216 ]. In addition, gene expression is also regulated via the interactions of RNA-binding proteins, namely with 5’-UTRs and 3’-UTRs, including their potential stem–loop–stem structures as discussed in the context of lens differentiation [ 147 , 217 , 218 ].…”

Section: Discussionmentioning

confidence: 99%

Multiomics Analysis Reveals Novel Genetic Determinants for Lens Differentiation, Structure, and Transparency

et al. 2023

View full text Add to dashboard Cite

Recent advances in next-generation sequencing and data analysis have provided new gateways for identification of novel genome-wide genetic determinants governing tissue development and disease. These advances have revolutionized our understanding of cellular differentiation, homeostasis, and specialized function in multiple tissues. Bioinformatic and functional analysis of these genetic determinants and the pathways they regulate have provided a novel basis for the design of functional experiments to answer a wide range of long-sought biological questions. A well-characterized model for the application of these emerging technologies is the development and differentiation of the ocular lens and how individual pathways regulate lens morphogenesis, gene expression, transparency, and refraction. Recent applications of next-generation sequencing analysis on well-characterized chicken and mouse lens differentiation models using a variety of omics techniques including RNA-seq, ATAC-seq, whole-genome bisulfite sequencing (WGBS), chip-seq, and CUT&RUN have revealed a wide range of essential biological pathways and chromatin features governing lens structure and function. Multiomics integration of these data has established new gene functions and cellular processes essential for lens formation, homeostasis, and transparency including the identification of novel transcription control pathways, autophagy remodeling pathways, and signal transduction pathways, among others. This review summarizes recent omics technologies applied to the lens, methods for integrating multiomics data, and how these recent technologies have advanced our understanding ocular biology and function. The approach and analysis are relevant to identifying the features and functional requirements of more complex tissues and disease states.

show abstract

“…Studies of the three-dimensional organization of the genome indicate that DNA looping between enhancers and promoters enables the integration of TF binding and cofactor recruitment from enhancers to promoters [20][21][22]. Some eRNAs functionally interact with factors that promote DNA-looping, including cohesin and mediator complexes and the ubiquitously-expressed TF YY1 [12,[23][24][25][26][27][28][29] to stimulate interaction between enhancers and target promoters (Figure 2A).…”

Section: Ernas Direct the Actorsmentioning

confidence: 99%