Prof Kazuhiro Maeshima - Chromatin behaviour in living cells revealed by single-nucleosome imaging скачать в хорошем качестве

Prof Kazuhiro Maeshima - Chromatin behaviour in living cells revealed by single-nucleosome imaging

The Cambridge BioSoc are excited to welcome our guest from Japan, Professor Kazuhiro Maeshima, a group leader at the National Institute of Genetics! Prof Maeshima is a biophysicist working on unravelling the 3D structure of mammalian genomes, thereby challenging established models found in textbooks. As he says: How chromatin is organized and behaves in living cells remains an important question in cell biology. Chromatin is a negatively charged long polymer consisting of genomic DNA, histones, and various non-histone proteins. Over the past ten years, newly developed technologies have drastically shifted our view on chromatin from a regular static structure to a more irregular and dynamic one (1). Using single-nucleosome imaging, we have revealed that chromatin is highly mobile and behaves locally like a liquid in living human cells. On the other hand, many factors, including chromatin-binding proteins, the transcriptional state, and cations, may influence chromatin behavior in living cells (2). Single-nucleosome imaging is a powerful tool to detect possible changes in the chromatin state induced by such factors (2). Using this imaging technique, we investigated genome-wide chromatin behavior under various transcriptional conditions in living human cells (3). While transcription by RNA polymerase II (RNAPII) is generally thought to need more open and dynamic chromatin, surprisingly, we found that active RNAPII globally constrains chromatin movements. RNAPII inhibition or RNAPII rapid depletion released the chromatin constraints and increased chromatin motion. Consistently, chromatin mobility also increased in quiescent G0 cells, which are transcriptionally less active. Furthermore, we recently showed that active RNA Pol I also form clusters and constrains ribosomal DNA (rDNA) chromatin in the nucleolus fibrillar center (FC)(4). Upon transcription inhibition, active Pol I dissociate from rDNA and move like a liquid in the "nucleolar caps" transformed from the FC. Our results suggest that chromatin is globally constrained by clustering of active RNA Pols, presumably for efficient gene transcription and regulation. References: 1. Maeshima, K. et al. (2019) Curr. Opin. Cell Biol. 58, 95–104. 2. Nozaki, T. et al. (2017) Mol. Cell. 67, 282-293. 3. Nagashima, R. et al. (2019) J. Cell Biol. 218, 1511–1530. 4. Ide, S. et al. (2020) Sci. Adv. 6, eabb5953. We look forward to welcoming him for this early lunchtime talk!