ChIP-Seq

Mediator is a well-known transcriptional co-regulator and serves as an adaptor between gene-specific regulatory proteins and RNA polymerase II. Studies on the chromatin-bound form of Mediator revealed interactions with additional protein complexes involved in various transcription-related processes, such as the Lsm2-8 complex that is part of the spliceosomal U6 small nuclear ribonucleoprotein complex. Here, we employ Chromatin Immunoprecipitation sequencing (ChIP-seq) of chromatin associated with the Lsm3 protein and the Med1 or Med15 Mediator subunits...

BACKGROUND: The nuclear lamina links the nuclear membrane to chromosomes and plays a crucial role in regulating chromatin states and gene expression. However, current knowledge of nuclear lamina in plants is limited compared to animals and humans. RESULTS: This study mainly focused on elucidating the mechanism through which the putative nuclear lamina component protein KAKU4 regulates chromatin states and gene expression in Arabidopsis leaves. Thus, we constructed a network using the association proteins of lamin-like proteins, revealing that KAKU4 is strongly associated with chromatin or epigenetic modifiers...

MOTIVATION: Aging is intricately linked to diseases and mortality. It is reflected in molecular changes across various tissues which can be leveraged for the development of biomarkers of aging using machine learning models, known as aging clocks. Despite advancements in the field, a significant challenge remains: the lack of robust, Python-based software tools for integrating and comparing these diverse models. This gap highlights the need for comprehensive solutions that can handle the complexity and variety of data in aging research...

BACKGROUND: Centromeres play a crucial and conserved role in cell division, although their composition and evolutionary history in green algae, the evolutionary ancestors of land plants, remains largely unknown. RESULTS: We constructed near telomere-to-telomere (T2T) assemblies for two Trebouxiophyceae species, Chlorella sorokiniana NS4-2 and Chlorella pyrenoidosa DBH, with chromosome numbers of 12 and 13, and genome sizes of 58.11 Mb and 53.41 Mb, respectively...

PRDM16 is a dynamic transcriptional regulator of various stem cell niches, including adipocytic, hematopoietic, cardiac progenitors, and neural stem cells. PRDM16 has been suggested to contribute to 1p36 deletion syndrome, one of the most prevalent subtelomeric microdeletion syndromes. We report a patient with a de novo nonsense mutation in the PRDM16 coding sequence, accompanied by lissencephaly and microcephaly features. Human stem cells were genetically modified to mimic this mutation, generating cortical organoids that exhibited altered cell cycle dynamics...

BACKGROUND: Enhancer RNAs (eRNAs) play a crucial role in transcriptional regulation. While significant progress has been made in understanding epigenetic regulation mediated by eRNAs, research on the construction of eRNA-mediated gene regulatory networks (eGRN) and the identification of critical network components that influence complex traits is lacking. RESULTS: Here, employing the pig as a model, we conducted a comprehensive study using H3K27ac histone ChIP-seq and RNA-seq data to construct eRNA expression profiles from multiple tissues of two distinct pig breeds, namely Enshi Black (ES) and Duroc...

Recent studies have uncovered that non-coding sequence variants may relate to Axenfeld-Rieger syndrome (ARS), a rare developmental anomaly with genetic heterogeneity. However, how these genomic regions are functionally and structurally associated with ARS is still unclear. In this study, we performed genome-wide linkage analysis and whole-genome sequencing in a Chinese ARS family and identified a heterozygous deletion of about 570 kb (termed LOH-1) in the intergenic sequence between PITX2 and FAM241A. Knockout of LOH-1 homologous sequences caused ARS phenotypes in mice...

Genetic sequencing has identified high-confidence ASD risk genes with loss-of-function mutations. How the haploinsufficiency of distinct ASD risk genes causes ASD remains to be elucidated. In this study, we examined the role of four top-ranking ASD risk genes, ADNP, KDM6B, CHD2, and MED13, in gene expression regulation. ChIP-seq analysis reveals that gene targets with the binding of these ASD risk genes at promoters are enriched in RNA processing and DNA repair. Many of these targets are found in ASD gene database (SFARI), and are involved in transcription regulation and chromatin remodeling...

Genetic variations in the glucocorticoid receptor (GR) gene NR3C1 can impact metabolism. The single nucleotide polymorphism (SNP) rs6190 (p.R23K) has been associated in humans with enhanced metabolic health, but the SNP mechanism of action remains completely unknown. We generated a transgenic knock-in mice genocopying this polymorphism to elucidate how the mutant GR impacts metabolism. Compared to non-mutant littermates, mutant mice showed increased muscle insulin sensitivity and strength on regular chow and high-fat diet, blunting the diet-induced adverse effects on weight gain and exercise intolerance...

BACKGROUND: Recent insights regarding mechanisms mediating stemness, heterogeneity, and metastatic potential of lung cancers have yet to be fully translated to effective regimens for the treatment of these malignancies. This study sought to identify novel targets for lung cancer therapy. METHODS: Transcriptomes and DNA methylomes of 14 SCLC and 10 NSCLC lines were compared to normal human small airway epithelial cells (SAEC) and induced pluripotent stem cell (iPSC) clones derived from SAEC...

A pervasive question in biological research studying gene regulation, chromatin structure, or genomics is where, and to what extent, does a signal of interest arise genome-wide? This question is addressed using a variety of methods relying on high-throughput sequencing data as their final output, including ChIP-seq for protein-DNA interactions [1], GapR-seq for measuring supercoiling [2], and HBD-seq or DRIP-seq for R-loop positioning [3,4]. Current computational methods to calculate genome-wide enrichment of the signal of interest usually do not properly handle the count-based nature of sequencing data, they often do not make use of the local correlation structure of sequencing data, and they do not apply any regularization of enrichment estimates...

Following the milestone success of the Human Genome Project, the 'Encyclopedia of DNA Elements (ENCODE)' initiative was launched in 2003 to unearth information about the numerous functional elements within the genome. This endeavor coincided with the emergence of numerous novel technologies, accompanied by the provision of vast amounts of whole-genome sequences, high-throughput data such as ChIP-Seq and RNA-Seq. Extracting biologically meaningful information from this massive dataset has become a critical aspect of many recent studies, particularly in annotating and predicting the functions of unknown genes...

UNLABELLED: Di- and tri-methylation of lysine 36 on histone H3 (H3K36me2/3) is catalysed by histone methyltransferase Set2, which plays an essential role in transcriptional regulation. Although there is a single H3K36 methyltransferase in yeast and higher eukaryotes, two H3K36 methyltransferases, Ash1 and Set2, were present in many filamentous fungi. However, their roles in H3K36 methylation and transcriptional regulation remained unclear. Combined with methods of RNA-seq and ChIP-seq, we revealed that both Ash1 and Set2 are redundantly required for the full H3K36me2/3 activity in Magnaporthe oryzae , which causes the devastating worldwide rice blast disease...

DNA motifs are crucial patterns in gene regulation. DNA-binding proteins (DBPs), including transcription factors, can bind to specific DNA motifs to regulate gene expression and other cellular activities. Past studies suggest that DNA shape features could be subtly involved in DNA-DBP interactions. Therefore, the shape motif annotations based on intrinsic DNA topology can deepen the understanding of DNA-DBP binding. Nevertheless, high-throughput tools for DNA shape motif discovery that incorporate multiple features altogether remain insufficient...

BACKGROUND: Repeat elements (REs) play important roles for cell function in health and disease. However, RE enrichment analysis in short-read high-throughput sequencing (HTS) data, such as ChIP-seq, is a challenging task. RESULTS: Here, we present RepEnTools, a software package for genome-wide RE enrichment analysis of ChIP-seq and similar chromatin pulldown experiments. Our analysis package bundles together various software with carefully chosen and validated settings to provide a complete solution for RE analysis, starting from raw input files to tabular and graphical outputs...

PURPOSE OF REVIEW: Ribosomal RNAs (rRNAs) are transcribed within nucleoli from rDNA repeats by RNA Polymerase I (Pol I). There is variation in rRNA transcription rates across the hematopoietic tree, and leukemic blast cells have prominent nucleoli, indicating abundant ribosome biogenesis. The mechanisms underlying these variations are poorly understood. The purpose of this review is to summarize findings of rDNA binding and Pol I regulation by hematopoietic transcription factors. RECENT FINDINGS: Our group recently used custom genome assemblies optimized for human and mouse rDNA mapping to map nearly 2200 ChIP-Seq datasets for nearly 250 factors to rDNA, allowing us to identify conserved occupancy patterns for multiple transcription factors...

Poor management and excess fertilization of apple (Malus domestica Borkh.) orchards are causing increasingly serious soil acidification, resulting in Al toxicity and direct poisoning of roots. Strigolactones (SLs) are reported to be involved in plant responses to abiotic stress, but their role and mechanism under AlCl3 stress remain unknown. Here, we found that applying 1 μm GR24 (an SL analoge) significantly alleviated AlCl3 stress of M26 apple rootstock, mainly by blocking the movement of Al through cell wall and by vacuolar compartmentalization of Al...

MOTIVATION: Automated chromatin segmentation based on ChIP-seq data reveals insights into the epigenetic regulation of chromatin accessibility. Existing segmentation methods are constrained by simplifying modeling assumptions, which may have a negative impact on the segmentation quality. RESULTS: We introduce EpiSegMix, a novel segmentation method based on a hidden Markov model with flexible read count distribution types and state duration modeling, allowing for a more flexible modeling of both histone signals and segment lengths...

BACKGROUND: Nucleosome repositioning in cancer is believed to cause many changes in genome organisation and gene expression. Understanding these changes is important to elucidate fundamental aspects of cancer. It is also important for medical diagnostics based on cell-free DNA (cfDNA), which originates from genomic DNA regions protected from digestion by nucleosomes. RESULTS: We have generated high-resolution nucleosome maps in paired tumour and normal tissues from the same breast cancer patients using MNase-assisted histone H3 ChIP-seq and compared them with the corresponding cfDNA from blood plasma...

UNLABELLED: Mutant isocitrate dehydrogenase 1 (mIDH1; IDH1 R132H ) exhibits a gain of function mutation enabling 2-hydroxyglutarate (2HG) production. 2HG inhibits DNA and histone demethylases, inducing epigenetic reprogramming and corresponding changes to the transcriptome. We previously demonstrated 2HG-mediated epigenetic reprogramming enhances DNA-damage response and confers radioresistance in mIDH1 gliomas harboring p53 and ATRX loss of function mutations. In this study, RNA-seq and ChIP-seq data revealed human and mouse mIDH1 glioma neurospheres have downregulated gene ontologies related to mitochondrial metabolism and upregulated autophagy...