Magnetorotational-type instability in Couette-Taylor flow of a viscoelastic polymer liquid

We describe an instability of viscoelastic Couette-Taylor flow that is directly analogous to the magnetorotational instability (MRI) in astrophysical magnetohydrodynamics, with polymer molecules playing the role of magnetic field lines. By determining the conditions required for the onset of instability and the properties of the preferred modes, we distinguish it from the centrifugal and elastic instabilities studied previously. Experimental demonstration and investigation should be much easier for the viscoelastic instability than for the MRI in a liquid metal. The analogy holds with the case of a predominantly toroidal magnetic field such as is expected in an accretion disk and it may be possible to access a turbulent regime in which many modes are unstable.Comment: 4 pages, 4 figures, to be published in Physical Review Letter

Mbd1 is recruited to both methylated and nonmethylated CpGs via distinct DNA binding domains

MBD1 is a vertebrate methyl-CpG binding domain protein (MBD) that can bring about repression of methylated promoter DNA sequences. Like other MBD proteins, MBD1 localizes to nuclear foci that in mice are rich in methyl-CpG. In methyl-CpG-deficient mouse cells, however, Mbd1 remains localized to heterochromatic foci whereas other MBD proteins become dispersed in the nucleus. We find that Mbd1a, a major mouse isoform, contains a CXXC domain (CXXC-3) that binds specifically to nonmethylated CpG, suggesting an explanation for methylation-independent localization. Transfection studies demonstrate that the CXXC-3 domain indeed targets nonmethylated CpG sites in vivo. Repression of nonmethylated reporter genes depends on the CXXC-3 domain, whereas repression of methylated reporters requires the MBD. Our findings indicate that MBD1 can interpret the CpG dinucleotide as a repressive signal in vivo regardless of its methylation status

Engineering a high-affinity methyl-CpG-binding protein

Core members of the MBD protein family (MeCP2, MBD1, MBD2 and MBD4) share a methyl-CpG-binding domain that has a specific affinity for methylated CpG sites in double-stranded DNA. By multimerizing the MDB domain of Mbd1, we engineered a poly-MBD protein that displays methyl-CpG-specific binding in vitro with a dissociation constant that is >50-fold higher than that of a monomeric MBD. Poly-MBD proteins also localize to methylated foci in cells and can deliver a functional domain to reporter constructs in vivo. We propose that poly-MBD proteins are sensitive reagents for the detection of DNA methylation levels in isolated native DNA and for cytological detection of chromosomal CpG methylatio

Genetic determinants of the epigenome in development and cancer

Although we have detailed maps of epigenetic marks on DNA and chromatin for many cell types and disease states, the origin and significance of these patterns is incompletely understood. Deregulation of the epigenome is a frequent accompaniment to cancer, and it is therefore important that we learn how it contributes to tumour formation. Here it is proposed that the roles of DNA sequence signals as determinants of the epigenome have been underappreciated. Taking as a paradigm the part played by the dinucleotide CpG in regulating gene expression via its effects on the epigenome, it is suggested that factors recognising other short, frequent sequence motifs also recruit chromatin modifying enzymes in response to DNA sequence. A screen for factors of this kind promises to aid our understanding of the mechanisms by which gene activity is globally regulated

Cfp1 integrates both CpG content and gene activity for accurate H3K4me3 deposition in embryonic stem cells

Trimethylation of histone H3 Lys 4 (H3K4me3) is a mark of active and poised promoters. The Set1 complex is responsible for most somatic H3K4me3 and contains the conserved subunit CxxC finger protein 1 (Cfp1), which binds to unmethylated CpGs and links H3K4me3 with CpG islands (CGIs). Here we report that Cfp1 plays unanticipated roles in organizing genome-wide H3K4me3 in embryonic stem cells. Cfp1 deficiency caused two contrasting phenotypes: drastic loss of H3K4me3 at expressed CGI-associated genes, with minimal consequences for transcription, and creation of “ectopic” H3K4me3 peaks at numerous regulatory regions. DNA binding by Cfp1 was dispensable for targeting H3K4me3 to active genes but was required to prevent ectopic H3K4me3 peaks. The presence of ectopic peaks at enhancers often coincided with increased expression of nearby genes. This suggests that CpG targeting prevents “leakage” of H3K4me3 to inappropriate chromatin compartments. Our results demonstrate that Cfp1 is a specificity factor that integrates multiple signals, including promoter CpG content and gene activity, to regulate genome-wide patterns of H3K4me3

Cohesin as an essential disruptor of chromosome organization

Cohesin is a multi-subunit molecular machine that is able to create lateral chromatin loops within a linear chromosome fiber. Despite intense study, a consensus view of the functional significance of loop extrusion has remained elusive. This perspective proposes a rationale based on the need for continual disruption of spurious higher-order chromatin secondary structures. It is argued that cohesin-mediated chromosomal churn ensures broad accessibility to the diffusible factors on which genome function depends

Loss of CpG island immunity to DNA methylation induced by mutation

The inheritance of acquired traits in mammals is a highly controversial topic in biology. Recently, Takahashi et al. (Cell 186:715–731, 2023) have reported that insertion of CpG-free DNA into a CpG island (CGI) can induce DNA methylation of the CGI and that this aberrant methylation pattern can be transmitted across generations, even after removal of the foreign DNA. These results were interpreted as evidence for transgenerational inheritance of acquired DNA methylation patterns. Here, we discuss several interpretational issues raised by this study and consider alternative explanations.</p