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Katznelson, A.* ; Hernandez, B.* ; Tapia, K.* ; Fahning, H.* ; Burton, A. ; Zhang, J.* ; Torres-Padilla, M.E. ; Plachta, N.* ; Zaret, K.S.* ; McCarthy, R.L.*

ERH elicits cell lineage restriction in mammalian preimplantation development and differentiation from pluripotency via H3K9me3-heterochromatin.

Nat. Commun. 17:9262 (2026)

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Enhancer of Rudimentary Homolog (ERH) is an evolutionarily conserved protein originally characterized as promoting fission yeast heterochromatin and recently shown to maintain H3K9me3 heterochromatin in human fibroblasts. Here, we find that ERH depletion in fibroblasts reverts the somatic cell H3K9me3 landscape of broad megabase size domains to an embryonic stem cell (ESC) state composed of mainly H3K9me3 peaks and enables activation of naïve and pluripotency genes and transposable elements during induced pluripotent stem cell (iPSC) reprogramming. Concordantly, we find that ERH represses totipotent and alternative lineage programs during mouse preimplantation development and is required for proper segregation of the inner cell mass and trophectoderm cell lineages. During human ESC differentiation into germ layer lineages, ERH silences naïve and pluripotency genes, transposable elements, and alternative lineage somatic genes. As in fission yeast, we find that mammalian ERH interacts with RNA-binding proteins to engage and repress its chromatin targets. Our findings reveal a conserved, fundamental role for ERH in mammalian cell fate specification via the initiation and maintenance of early developmental gene repression.

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Publication type Article: Journal article

Document type Scientific Article

Keywords Lineage (genetic) ; Cell Lineage ; Cell ; Cellular Differentiation ; Embryo

ISSN (print) / ISBN 2041-1723

e-ISSN 2041-1723

Journal Nature Communications

Quellenangaben Volume: 17, Article Number: 9262

Publisher Springer

Publishing Place London

Reviewing status Peer reviewed

Institute(s) Institute of Epigenetics and Stem Cells (IES)