Epigenomic anomalies contribute significantly to the development of numerous human disorders. The development of epigenetic research tools is essential for understanding how epigenetic marks contri... Tweetable abstract CRISPR/Cas9 system has been remodeled for epigenome editing by juxtaposing ‘dead’ dCas9 with an epigenetic effector domain. This tool has applications in cancer treatment and reg...

Clustering is an unsupervised approach to classify elements based on their similarity, and it is used to find the intrinsic patterns of data. There are enormous applications of clustering in bioinformatics, pattern recognition, and astronomy. This paper presents a clustering approach based on the idea that density wise single or multiple connected regions make a cluster, in which density maxima point represents the center of the corresponding density region. More precisely, our approach firstly finds the local density regions and subsequently merges the density connected regions to form the meaningful clusters. This idea empowers the clustering procedure, in which outliers are automatically detected, higher dense regions are intuitively determined and merged to form clusters of arbitrary shape, and clusters are identified regardless the dimensionality of space in which they are embedded. Extensive experiments are performed on several complex data sets to analyze and compare our approach with the state-of-the-art clustering methods. In addition, we benchmarked the algorithm on gene expression microarray data sets for cancer subtyping; to distinguish normal tissues from tumor; and to classify multiple tissue data sets.

As cells enter mitosis, chromatin compacts to facilitate chromosome segregation yet remains transcribed. Transcription supercoils DNA to levels that can impede further progression of RNA polymerase II (RNAPII) unless it is removed by DNA topoisomerase 1 (TOP1). Using ChIP-seq on mitotic cells, we found that TOP1 is required for RNAPII translocation along genes. The stimulation of TOP1 activity by RNAPII during elongation allowed RNAPII clearance from genes in prometaphase and enabled chromosomal segregation. Disruption of the TOP1-RNAPII interaction impaired RNAPII spiking at promoters and triggered defects in the post-mitotic transcription program. This program includes factors necessary for cell growth, and cells with impaired TOP1-RNAPII interaction are more sensitive to inhibitors of mTOR signaling. We conclude that TOP1 is necessary for assisting transcription during mitosis with consequences for growth and gene expression long after mitosis is completed. In this sense, TOP1 ensures that cellular memory is preserved in subsequent generations.

N6-methyladenosine (m6A) is an RNA modification wherein the N6-position of adenosine is methylated. It is one of the most prevalent internal modifications of RNA and regulates various aspects of RNA metabolism. M6A is deposited by m6A methyltransferases, removed by m6A demethylases, and recognized by reader proteins, which modulate splicing, export, translation, and stability of the modified mRNA. Recent evidence suggests that various classes of noncoding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long con-coding RNAs (lncRNAs), are also targeted by this modification. Depending on the ncRNA species, m6A may affect the processing, stability, or localization of these molecules. The m6Amodified ncRNAs are implicated in a number of diseases, including cancer. In this review, the author summarizes the role of m⁶A modification in the regulation and functions of ncRNAs in tumor development. Moreover, the potential applications in cancer prognosis and therapeutics are discussed.

Abnormal WNT signaling increases MYC expression in colon cancer cells in part via oncogenic super-enhancer-(OSE)-mediated gating of the active MYC to the nuclear pore in a poorly understood process. We show here that the principal tenet of the WNT-regulated MYC gating, facilitating nuclear export of the MYC mRNA, is regulated by a CTCF binding site (CTCFBS) within the OSE to confer growth advantage in HCT-116 cells. To achieve this, the CTCFBS directs the WNT-dependent trafficking of the OSE to the nuclear pore from intra-nucleoplasmic positions in a stepwise manner. Once the OSE reaches a peripheral position, which is triggered by a CTCFBS-mediated CCAT1 eRNA activation, its final stretch (≤0.7 μm) to the nuclear pore requires the recruitment of AHCTF1, a key nucleoporin, to the CTCFBS. Thus, a WNT/ß-catenin-AHCTF1-CTCF-eRNA circuit enables the OSE to promote pathological cell growth by coordinating the trafficking of the active MYC gene within the 3D nuclear architecture.