Biology subjects

Choi, J. E.

Publications and source records attributed to Choi, J. E..

3 recordsLinked to original sources

bioRxiv2020

Synaptic correlates of associative fear memory in the lateral amygdala

Successful adaptation to the environment requires accurate responding to external threats by recalling specific memories. However, elucidating underlying neural substrates of associative fear memory was limited due to the difficulties in direct examination of extinction-induced changes of specific synapses that encode an auditory fear memory. Using dual-eGRASP (enhanced Green Fluorescent Protein Reconstitution Across Synaptic Partners), we found that synapses between engram cells or synaptic engram showed a significantly larger spine morphology at auditory cortex (AC) to lateral amygdala (LA) projections after auditory fear conditioning. Fear extinction reversed the enhanced synaptic engram spines while re-conditioning with the same tone and shock restored the size of the synaptic engram. Taken together, we suggest that the synaptic engram may represent a different state of fear memory. One Sentence SummaryAssociative fear memory enlarged the spine morphology of synapses between engram neurons in the amygdala, which was diminished by memory extinction and restored by re-conditioning, suggesting that connections between engram cells represent a different state of fear memory.

neuroscience↗

bioRxiv2020

KIAA1841, a novel SANT and BTB domain-containing protein, inhibits class switch recombination

Class switch recombination (CSR) enables B cells to produce different immunoglobulin isotypes and mount an effective immune response against pathogens. Timely resolution of CSR prevents damage due to an uncontrolled and prolonged immune response. While many positive regulators of CSR have been described, negative regulators of CSR are relatively unknown. Using a shRNA library screen in a mouse B cell line, we have identified the novel protein KIAA1841 (NM_027860) as a negative regulator of CSR. KIAA1841 is an uncharacterized protein of 82kD containing SANT and BTB domains. The BTB domain of KIAA1841 exhibited characteristic properties such as self-dimerization and interaction with co-repressor proteins. Overexpression of KIAA1841 inhibited CSR in primary mouse splenic B cells, and inhibition of CSR is dependent on the BTB domain while the SANT domain is largely dispensable. Thus, we have identified a new member of the BTB family that serves as a negative regulator of CSR.

molecular biology↗

bioRxiv2020

Merkel cell polyomavirus in Merkel cell carcinoma: Integration sites and involvement of the KMT2D tumor suppressor gene

Merkel cell carcinoma (MCC) is an uncommon, lethal cancer of the skin caused by either Merkel cell polyomavirus (MCV) or UV-linked mutations. MCV is found integrated into MCC tumor genomes, accompanied by truncation mutations that render the MCV large T antigen replication incompetent. We used the open access HPV Detector/ Cancervirus Detector tool to determine the MCV integration sites in whole exome sequencing data from 5 MCC cases, thereby adding to the limited published MCV integration site junction data. We also systematically reviewed published data on integration for MCV in the human genome, presenting a collation of 123 MCC cases and their linked chromosomal sites. We confirm that there are no highly recurrent specific sites of integration. We found that, chromosome 5 is the chromosome most frequently involved by MCV integration and that integration sites are significantly enriched for genes with binding sites for oncogenic transcription factors such as LEF1 and ZEB1, suggesting the possibility of increased open chromatin in these gene sets. Additionally, in one case we found integration involving the tumor suppressor gene KMT2D for the first time, adding to previous reports of rare MCV integration into host tumor suppressor genes in MCC.

cancer biology↗