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The multifunctional zinc‐finger protein CCCTC‐binding factor (CTCF) is a very strong candidate for the role of coordinating the expression level of coding sequences with their three‐dimensional position in the nucleus, apparently responding to a “code” in the DNA itself. Dynamic interactions between chromatin fibers in the context of nuclear architecture have been implicated in various aspects of...
Does the three‐dimensional (3D) conformation of interphase chromosomes merely reflect their function or does it actively contribute to gene regulation? The analysis of sex chromosomes that are subject to chromosome‐wide dosage compensation processes promises new insight into this question. Chromosome conformations are dynamic and largely determined by association of distant chromosomal loci in the...
Epigenetic modifications, such as DNA methylation and post‐translation modifications of histones, have been shown to play an important role in chromatin structure, promoter activity, and cellular reprogramming. Large protein complexes, such as Polycomb and trithorax, often harbor multiple activities which affect histone tail modification. Nevertheless, the mechanisms underlying the deposition of these...
Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can self‐renew indefinitely and contribute to all tissue types of the adult organism. Stem cell‐based therapeutic approaches hold enormous promise for the cure of regenerative diseases. Over the last few years, several studies have attempted to decipher the important role of transcription factor networks and epigenetic regulatory...
High‐throughput genomic sequencing and quantitative mass spectrometry (MS)‐based proteomics technology have recently emerged as powerful tools, increasing our understanding of chromatin structure and function. Both of these approaches require substantial investments and expertise in terms of instrumentation, experimental methodology, bioinformatics, and data interpretation and are, therefore, usually...
Recent systematic studies using newly developed genomic approaches have revealed common mechanisms and principles that underpin the spatial organization of eukaryotic genomes and allow them to respond and adapt to diverse functional demands. Genomes harbor, interpret, and propagate genetic and epigenetic information, and the three‐dimensional (3D) organization of genomes in the nucleus should be intrinsically...
Endogenous retrovirsuses (ERVs) have long been known to influence gene expression in plants in important ways, but what of their roles in mammals? Our relatively sparse knowledge in that area was recently increased with the finding that ERVs can influence the expression of mammalian resident genes by disrupting transcriptional termination. For many mammalian biologists, retrotransposition is considered...
Mixed lineage leukemia (MLL) fusion protein (FP)‐induced acute leukemia is highly aggressive and often refractory to therapy. Recent progress in the field has unraveled novel mechanisms and targets to combat this disease. Menin, a nuclear protein, interacts with wild‐type (WT) MLL, MLL‐FPs, and other partners such as the chromatin‐associated protein LEDGF and the transcription factor C‐Myb to promote...
How fast? How strong? How many? So what? Why do numbers matter in biology? Chromatin binding proteins are forever in motion, exchanging rapidly between bound and free pools. How do regulatory systems whose components are in constant flux ensure stability and flexibility? This review explores the application of quantitative and mathematical approaches to mechanisms of epigenetic regulation. We discuss...
Genomic function is dictated by a combination of DNA sequence and the molecular mechanisms controlling access to genetic information. Access to DNA can be determined by the interpretation of covalent modifications that influence the packaging of DNA into chromatin, including DNA methylation and histone modifications. These modifications are believed to be forms of “epigenetic codes” that exist in...
The nuclear envelope shapes the functional organization of the nucleus. Increasing evidence indicates that one of its main components, the nuclear lamina, dynamically interacts with the genome, including the promoter region of specific genes. This seems to occur in a manner that accords developmental significance to these interactions. This essay addresses key issues raised by recent data on the association...
Understanding the functional mechanisms underlying genetic signals associated with complex traits and common diseases, such as cancer, diabetes and Alzheimer's disease, is a formidable challenge. Many genetic signals discovered through genome‐wide association studies map to non‐protein coding sequences, where their molecular consequences are difficult to evaluate. This article summarizes concepts...
While large portions of the mammalian genome are known to replicate sequentially in a distinct, tissue‐specific order, recent studies suggest that the inactive X chromosome is duplicated rapidly via random, synchronous DNA synthesis at numerous adjacent regions. The rapid duplication of the inactive X chromosome was observed in high‐resolution studies visualizing DNA replication patterns in the nucleus,...
Histone post‐translational modifications (PTMs) alter the chromatin architecture, generating “open” and “closed” states, and these structural changes can modulate gene expression under specific cellular conditions. While methylation and acetylation are the best‐characterized histone PTMs, citrullination by the protein arginine deiminases (PADs) represents another important player in this process....
Disruptions in chromatin regulator genes are frequently the cause of neurodevelopmental and neuropsychiatric disorders. Chromatin regulators are widely expressed in the brain, yet symptoms suggest that specific circuits can be preferentially altered when they are mutated. Using Drosophila allows targeted manipulation of chromatin regulators in defined neuronal classes, lineages, or circuits, revealing...
The chromatin fiber consists of a string of nucleosomes connected by linker DNA regions. The hierarchy of folding of this fiber within the cell has long been controversial, and the existence of an originally described 30 nm fiber has been debated and reviewed extensively. This review contextualizes two recent papers on this topic that suggest the 30 nm fiber to be an over‐simplification. The idealized...
Gene transcription is strictly controlled by the interplay of regulatory events at gene promoters and gene‐distal regulatory elements called enhancers. Despite extensive studies of enhancers, we still have a very limited understanding of their mechanisms of action and their restricted spatio‐temporal activities. A better understanding would ultimately lead to fundamental insights into the control...
Chromosomes are not only carriers of the genetic material, but also actively regulate the assembly of complex intracellular architectures. During mitosis, chromosome‐induced microtubule polymerisation ensures spindle assembly in cells without centrosomes and plays a supportive role in centrosome‐containing cells. Chromosomal signals also mediate post‐mitotic nuclear envelope (NE) re‐formation. Recent...
While N6‐methyladenosine (m6A) is a well‐known epigenetic modification in bacterial DNA, it remained largely unstudied in eukaryotes. Recent studies have brought to fore its potential epigenetic role across diverse eukaryotes with biological consequences, which are distinct and possibly even opposite to the well‐studied 5‐methylcytosine mark. Adenine methyltransferases appear to have been independently...
The DNase I hypersensitive sites (DHSs) of chromatin constitute one of the best landmarks of eukaryotic genes that are poised and/or activated for transcription. For over 35 years, the high‐mobility group nucleosome‐binding chromosomal proteins HMGN1 and HMGN2 have been shown to play a role in the establishment of these chromatin‐accessible domains at transcriptional regulatory elements, namely promoters...
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