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1. Evolutionary Dynamics of Chromatin Structure and Duplicate Gene Expression in Diploid and Allopolyploid Cotton

   https://doi.org/10.1093/molbev/msae095  

   Hu, Guanjing; Grover, Corrinne E; Vera, Daniel L; Lung, Pei-Yau; Girimurugan, Senthil B; Miller, Emma R; Conover, Justin L; Ou, Shujun; Xiong, Xianpeng; Zhu, De; et al (May 2024, Molecular Biology and Evolution)

   Purugganan, Michael (Ed.)

   Polyploidy is a prominent mechanism of plant speciation and adaptation, yet the mechanistic understandings of duplicated gene regulation remain elusive. Chromatin structure dynamics are suggested to govern gene regulatory control. Here, we characterized genome-wide nucleosome organization and chromatin accessibility in allotetraploid cotton, Gossypium hirsutum (AADD, 2n = 4X = 52), relative to its two diploid parents (AA or DD genome) and their synthetic diploid hybrid (AD), using DNS-seq. The larger A-genome exhibited wider average nucleosome spacing in diploids, and this intergenomic difference diminished in the allopolyploid but not hybrid. Allopolyploidization also exhibited increased accessibility at promoters genome-wide and synchronized cis-regulatory motifs between subgenomes. A prominent cis-acting control was inferred for chromatin dynamics and demonstrated by transposable element removal from promoters. Linking accessibility to gene expression patterns, we found distinct regulatory effects for hybridization and later allopolyploid stages, including nuanced establishment of homoeolog expression bias and expression level dominance. Histone gene expression and nucleosome organization are coordinated through chromatin accessibility. Our study demonstrates the capability to track high-resolution chromatin structure dynamics and reveals their role in the evolution of cis-regulatory landscapes and duplicate gene expression in polyploids, illuminating regulatory ties to subgenomic asymmetry and dominance. 

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2. Depletion of lamins B1 and B2 promotes chromatin mobility and induces differential gene expression by a mesoscale-motion-dependent mechanism

   https://doi.org/10.1186/s13059-024-03212-y  

   Pujadas_Liwag, Emily M; Wei, Xiaolong; Acosta, Nicolas; Carter, Lucas M; Yang, Jiekun; Almassalha, Luay M; Jain, Surbhi; Daneshkhah, Ali; Rao, Suhas_S P; Seker-Polat, Fidan; et al (December 2024, Genome Biology)

   Abstract BackgroundB-type lamins are critical nuclear envelope proteins that interact with the three-dimensional genomic architecture. However, identifying the direct roles of B-lamins on dynamic genome organization has been challenging as their joint depletion severely impacts cell viability. To overcome this, we engineered mammalian cells to rapidly and completely degrade endogenous B-type lamins using Auxin-inducible degron technology. ResultsUsing live-cell Dual Partial Wave Spectroscopic (Dual-PWS) microscopy, Stochastic Optical Reconstruction Microscopy (STORM), in situ Hi-C, CRISPR-Sirius, and fluorescence in situ hybridization (FISH), we demonstrate that lamin B1 and lamin B2 are critical structural components of the nuclear periphery that create a repressive compartment for peripheral-associated genes. Lamin B1 and lamin B2 depletion minimally alters higher-order chromatin folding but disrupts cell morphology, significantly increases chromatin mobility, redistributes both constitutive and facultative heterochromatin, and induces differential gene expression both within and near lamin-associated domain (LAD) boundaries. Critically, we demonstrate that chromatin territories expand as upregulated genes within LADs radially shift inwards. Our results indicate that the mechanism of action of B-type lamins comes from their role in constraining chromatin motion and spatial positioning of gene-specific loci, heterochromatin, and chromatin domains. ConclusionsOur findings suggest that, while B-type lamin degradation does not significantly change genome topology, it has major implications for three-dimensional chromatin conformation at the single-cell level both at the lamina-associated periphery and the non-LAD-associated nuclear interior with concomitant genome-wide transcriptional changes. This raises intriguing questions about the individual and overlapping roles of lamin B1 and lamin B2 in cellular function and disease. 

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3. Lamin A/C Is Dispensable to Mechanical Repression of Adipogenesis

   https://doi.org/10.3390/ijms22126580  

   Goelzer, Matthew; Dudakovic, Amel; Olcum, Melis; Sen, Buer; Ozcivici, Engin; Rubin, Janet; van Wijnen, Andre J.; Uzer, Gunes (June 2021, International Journal of Molecular Sciences)

   null (Ed.)

   Mesenchymal stem cells (MSCs) maintain the musculoskeletal system by differentiating into multiple lineages, including osteoblasts and adipocytes. Mechanical signals, including strain and low-intensity vibration (LIV), are important regulators of MSC differentiation via control exerted through the cell structure. Lamin A/C is a protein vital to the nuclear architecture that supports chromatin organization and differentiation and contributes to the mechanical integrity of the nucleus. We investigated whether lamin A/C and mechanoresponsiveness are functionally coupled during adipogenesis in MSCs. siRNA depletion of lamin A/C increased the nuclear area, height, and volume and decreased the circularity and stiffness. Lamin A/C depletion significantly decreased markers of adipogenesis (adiponectin, cellular lipid content) as did LIV treatment despite depletion of lamin A/C. Phosphorylation of focal adhesions in response to mechanical challenge was also preserved during loss of lamin A/C. RNA-seq showed no major adipogenic transcriptome changes resulting from LIV treatment, suggesting that LIV regulation of adipogenesis may not occur at the transcriptional level. We observed that during both lamin A/C depletion and LIV, interferon signaling was downregulated, suggesting potentially shared regulatory mechanism elements that could regulate protein translation. We conclude that the mechanoregulation of adipogenesis and the mechanical activation of focal adhesions function independently from those of lamin A/C. 

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4. Humanized nucleosomes reshape replication initiation and rDNA/nucleolar integrity in yeast

   https://doi.org/10.1101/2023.05.06.539710  

   Lazar-Stefanita, Luciana; Haase, Max_A B; Boeke, Jef D (May 2023, bioRxiv)

   Summary Eukaryotic DNA wraps around histone octamers forming nucleosomes, which modulate genome function by defining chromatin environments with distinct accessibility. These well-conserved properties allowed “humanization” of the nucleosome core particle (NCP) inSaccharomyces cerevisiaeat high fitness costs. Here we studied nucleosome-humanized yeast-genomes to understand how species-specific chromatin affects nuclear organization and function. We found a size increase in human-NCP, linked to shorter free linker DNA, supporting decreased chromatin accessibility. 3-D humanized-genome maps showed increased chromatin compaction and defective centromere clustering, correlated with high chromosomal aneuploidy rate. Site-specific chromatin alterations were associated with lack of initiation of early origins of replication and dysregulation of the ribosomal (rDNA and rRNA) metabolism. This latter led to nucleolar fragmentation and rDNA-array instability, through a non-coding RNA dependent mechanism, leading to its extraordinary, but entirely reversible, intra-chromosomal expansion. Overall, our results reveal species-specific properties of the NCP that define epigenome function across vast evolutionary distances. HighlightsHumanized nucleosomes wrap 10 additional nucleotides, shortening free linker lengthHistone-humanized nucleosomes have increased occupancy for DNAHumanized nucleosomes potentially decrease chromatin accessibility by blocking-out free linker DNANucleosome humanization impedes DNA replication by affecting chromatin structure at originsHumanized nucleosomes reversibly destabilize the ribosomal DNA array and leads to massive intrachromosomal rDNA locus expansionHistone humanization disrupts rDNA silencing and leads to nucleolar fragmentation 

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5. An AT-hook transcription factor promotes transcription of histone, spliced-leader, and piRNA clusters

   https://doi.org/10.1093/nar/gkaf079  

   Wang, Yi-Hui; Hertz, Hannah L; Pastore, Benjamin; Tang, Wen (February 2025, Nucleic Acids Research)

   Abstract In all three domains of life, genes with related functions can be organized into specific genomic regions known as gene clusters. In eukaryotes, histone, piRNA (Piwi-interacting RNA), and rDNA (ribosomal DNA) clusters are among the most notable clusters which play fundamental roles in chromatin formation, genome integrity, and translation, respectively. These clusters have long been thought to be regulated by distinct transcriptional mechanisms. In this study, using Caenorhabditis elegans as a model system we identify ATTF-6, a member of the AT-hook family, as a key factor for the expression of histone, piRNA, and 5S rDNA-SL1 (spliced leader 1) clusters. ATTF-6 is essential for C. elegans viability. It forms distinct nuclear foci at both piRNA and 5S rDNA-SL1 clusters. Loss of ATTF-6 leads to a depletion of histone mRNAs, SL1 transcripts, and piRNAs. Additionally, we demonstrate that ATTF-6 is required for the recruitment of USTC (Upstream Sequence Transcription Complex) to piRNA clusters, which is necessary for piRNA production. Collectively, our findings reveal a unifying role for an AT-hook transcription factor in promoting the expression of fundamental gene clusters. 

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