Talks

Genomic imprinting is observed in endosperm, a placenta-like seed tissue, where transposable elements (TEs) and repeat-derived small(s)RNAs mediate epigenetic changes in plants. In imprinting, uniparental gene expression arises due to parent-specific epigenetic marks on one allele but not on the other. The importance of sRNAs and their regulation in endosperm development or in imprinting is poorly understood in crops. Here we show that a previously uncharacterized CLASSY (CLSY)-family chromatin remodeler named OsCLSY3 is essential for rice endosperm development and imprinting, acting as an upstream player in sRNA pathway. Comparative transcriptome and genetic analysis indicated its endosperm-preferred expression and its paternally imprinted nature. These important features were modulated by RNA-directed DNA methylation (RdDM) of tandemly arranged TEs in its promoter. Upon perturbation of OsCLSY3 in transgenic lines we observed defects in endosperm development and loss of around 70% of ...

Chromatin is organized hierarchically at multiple scales and this is crucial for the spatiotemporal regulation of transcription. The fundamental units of nuclear organization are the highly self-interacting regions of chromatin termed as ‘Topologically Associated Domains’ or TADs. TADs are formed by a loop-extrusion mechanism mediated by two proteins: cohesin and CTCF. The major function of these units is to limit the action of regulatory elements to genes within the same TAD. Disruption of TAD boundaries can lead to dysregulation of gene expression and accessibility with a dramatic phenotypic consequence on developmental processes and pathogenesis Given the importance of CTCF in the formation of TADs and the role of the latter in gene regulation, it is not surprising that mutation in this protein have been reported in several diseases. While CTCF is a ubiquitously expressed, essential protein, it has a paralogue; CTCFL with a similar DNA binding domain that is normally expressed only ...

B cells undergoing physiologically programmed or aberrant genomic alterations provide an opportune system to study the causes and consequences of genome mutagenesis. Activated B cells in germinal centers express activation-induced cytidine deaminase (AID) to accomplish physiological somatic hypermutation (SHM) of their antibody-encoding genes. In attempting to diversify their immunoglobulin (Ig) heavy- and light-chain genes, several B-cell clones successfully optimize their antigen-binding affinities. However, SHM can sometimes occur at non-Ig loci, causing genetic alternations that lay the foundation for lymphomagenesis, particularly diffuse large B-cell lymphoma. Thus, SHM acts as a double-edged sword, bestowing superb humoral immunity at the potential risk of initiating disease. We refer to off-target, non-Ig AID mutations - that are often but not always associated with disease - as aberrant SHM (aSHM). A key challenge in understanding SHM and aSHM is determining how AID targets and...