Genomic imprinting is a phenomenon that restricts transcription to predominantly one parental allele. How this transcriptional duality is regulated is poorly understood. Here we perform an RNA interference screen for epigenetic factors involved in paternal allelic silencing at the Kcnq1ot1 imprinted domain in mouse extraembryonic endoderm stem cells. Multiple factors are identified, including nucleoporin 107 (NUP107). To determine NUP107’s role and specificity in Kcnq1ot1 imprinted domain regulation, we deplete Nup107, as well as Nup62, Nup98/96 and Nup153. Nup107, Nup62 and Nup153, but not Nup98/96 depletion, reduce Kcnq1ot1 noncoding RNA volume, displace the Kcnq1ot1 domain from the nuclear periphery, reactivate a subset of normally silent paternal alleles in the domain, alter histone modifications with concomitant changes in KMT2A, EZH2 and EHMT2 occupancy, as well as reduce cohesin interactions at the Kcnq1ot1 imprinting control region. Our results establish an important role for specific nucleoporins in mediating Kcnq1ot1 imprinted domain regulation.

Rectal carcinoma with metastasis to skeletal muscle is rare. So far, 16 cases of skeletal muscle metastasis from colorectal carcinoma have been documented of which only 5 were rectal carcinomas.[1] We discuss here the case of a 69-year old male, a known case of mucinous adenocarcinoma status post neoadjuvant chemoradiotherapy and abdomino perineal resection, who presented with low backache 4 months post surgery. He was found to have metastasis to multiple skeletal muscles without the involvement of common sites, such as liver and lung. The role of 18-FDG–PET/CT in such cases is rarely reported in the literature. This case highlights the importance of utilizing 18-FDG-PET/CT in detecting sites of skeletal muscle metastasis and thereby guides appropriate management.

Recently, many advancements in genome-wide chromatin topology and nuclear architecture have unveiled the complex and hidden world of the nucleus, where chromatin is organized into discrete neighbourhoods with coordinated gene expression. This includes the active and inactive X chromosomes. Using X chromosome inactivation as a working model, we utilized publicly available datasets together with a literature review to gain insight into topologically associated domains, lamin-associated domains, nucleolar-associating domains, scaffold/matrix attachment regions, and nucleoporin-associated chromatin and their role in regulating monoallelic expression. Furthermore, we comprehensively review for the first time the role of chromatin topology and nuclear architecture in the regulation of genomic imprinting. We propose that chromatin topology and nuclear architecture are important regulatory mechanisms for directing gene expression within imprinted domains. Furthermore, we predict that dynamic changes in chromatin topology and nuclear architecture play roles in tissue-specific imprint domain regulation during early development and differentiation.

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Head and neck paragangliomas (HNPGLs) are rare, rarely functional tumors known to have a genetic predisposition. Carotid body tumors (CBT) are the most common HNPGLs followed by jugular bulb tumors, vagus nerve, and tympanic plexus. The prevertebral region is not the known area for these tumors as seen in our case making it a rare case. Mutations in SDH-D linked genes are commonly associated with multiple HNPGLs. SDH-D mutations with single-gene deletion are rare as seen in the present case. Bilateral carotid body tumors need to be managed in a staged manner. Patients with HNPGLs need annual clinical, hormonal, and radiological, surveillance for early diagnosis and management. First-degree relatives, especially males, need surveillance as SDH-D mutations exhibit maternal imprinting. We describe here the management of a middleaged male who came with neck swelling on evaluation and was found to have nonfunctional bilateral carotid body tumors, mediastinal, and a rare prevertebral tiny lesion.