N M E Fogarty1, G J Burton2, A C Ferguson-Smith3. 1. Centre for Trophoblast Research, Department of Physiology Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK; The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, London, NW7 1AA, UK. Electronic address: Norah.Fogarty@crick.ac.uk. 2. Centre for Trophoblast Research, Department of Physiology Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK. 3. Centre for Trophoblast Research, Department of Physiology Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK; Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, UK.
Abstract
INTRODUCTION: The syncytiotrophoblast (STB) epithelial covering of the villous tree in the human placenta is a multi-nucleated syncytium that is sustained by continuous incorporation of differentiating cytotrophoblast (CTB) cells. STB nuclei display a variety of morphologies, but are generally more condensed in comparison to CTB nuclei. Here, we consider whether this condensation is a feature of epigenetic regulation of chromatin structure. METHODS: Semi-quantitative immunohistochemical investigations of a panel of histone modifications were performed to determine the relative proportions in CTB and STB nuclear populations. We also investigated the patterns of DNA methylation and distribution of DNA methyltransferases enzymes in these populations. RESULTS: Unexpectedly DNA methylation, and H3K9me3 and H3K27me3, which are modifications associated with heterochromatin, are present at lower levels in STB nuclei compared to CTB, despite the intensive condensation in the former nuclear population and the progenitor state of the latter. By contrast, STB nuclei are enriched for H4K20me3, which is also associated with repressive states. 5'hydroxymethylcytosine immunoreactivity is higher in STB, with intense staining observed in the highly condensed nuclei within syncytial knots. DISCUSSION: Cell-type specific epigenetic states exist within the trophoblast populations potentially regulating their different functions and developmental properties and suggesting non-canonical epigenetic states associated with the properties of these cells.
INTRODUCTION: The syncytiotrophoblast (STB) epithelial covering of the villous tree in the human placenta is a multi-nucleated syncytium that is sustained by continuous incorporation of differentiating cytotrophoblast (CTB) cells. STB nuclei display a variety of morphologies, but are generally more condensed in comparison to CTB nuclei. Here, we consider whether this condensation is a feature of epigenetic regulation of chromatin structure. METHODS: Semi-quantitative immunohistochemical investigations of a panel of histone modifications were performed to determine the relative proportions in CTB and STB nuclear populations. We also investigated the patterns of DNA methylation and distribution of DNA methyltransferases enzymes in these populations. RESULTS: Unexpectedly DNA methylation, and H3K9me3 and H3K27me3, which are modifications associated with heterochromatin, are present at lower levels in STB nuclei compared to CTB, despite the intensive condensation in the former nuclear population and the progenitor state of the latter. By contrast, STB nuclei are enriched for H4K20me3, which is also associated with repressive states. 5'hydroxymethylcytosine immunoreactivity is higher in STB, with intense staining observed in the highly condensed nuclei within syncytial knots. DISCUSSION: Cell-type specific epigenetic states exist within the trophoblast populations potentially regulating their different functions and developmental properties and suggesting non-canonical epigenetic states associated with the properties of these cells.
Authors: Rebecca L Wilson; Maxime François; Tanja Jankovic-Karasoulos; Dale McAninch; Dylan McCullough; Wayne R Leifert; Claire T Roberts; Tina Bianco-Miotto Journal: Epigenetics Date: 2019-04-30 Impact factor: 4.528
Authors: Todd M Everson; Marta Vives-Usano; Emie Seyve; Johanna Lepeule; Marie-France Hivert; Mariona Bustamante; Andres Cardenas; Marina Lacasaña; Jeffrey M Craig; Corina Lesseur; Emily R Baker; Nora Fernandez-Jimenez; Barbara Heude; Patrice Perron; Beatriz Gónzalez-Alzaga; Jane Halliday; Maya A Deyssenroth; Margaret R Karagas; Carmen Íñiguez; Luigi Bouchard; Pedro Carmona-Sáez; Yuk J Loke; Ke Hao; Thalia Belmonte; Marie A Charles; Jordi Martorell-Marugán; Evelyne Muggli; Jia Chen; Mariana F Fernández; Jorg Tost; Antonio Gómez-Martín; Stephanie J London; Jordi Sunyer; Carmen J Marsit Journal: Nat Commun Date: 2021-08-24 Impact factor: 14.919