A cis-acting mechanism mediates transcriptional memory at Polycomb target genes in mammals
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A cis-acting mechanism mediates transcriptional memory at Polycomb target genes in mammals. / Holoch, Daniel; Wassef, Michel; Lövkvist, Cecilia; Zielinski, Dina; Aflaki, Setareh; Lombard, Bérangère; Héry, Tiphaine; Loew, Damarys; Howard, Martin; Margueron, Raphaël.
I: Nature Genetics, Bind 53, 2021, s. 1686-1697.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - A cis-acting mechanism mediates transcriptional memory at Polycomb target genes in mammals
AU - Holoch, Daniel
AU - Wassef, Michel
AU - Lövkvist, Cecilia
AU - Zielinski, Dina
AU - Aflaki, Setareh
AU - Lombard, Bérangère
AU - Héry, Tiphaine
AU - Loew, Damarys
AU - Howard, Martin
AU - Margueron, Raphaël
N1 - Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021
Y1 - 2021
N2 - Epigenetic inheritance of gene expression states enables a single genome to maintain distinct cellular identities. How histone modifications contribute to this process remains unclear. Using global chromatin perturbations and local, time-controlled modulation of transcription, we establish the existence of epigenetic memory of transcriptional activation for genes that can be silenced by the Polycomb group. This property emerges during cell differentiation and allows genes to be stably switched after a transient transcriptional stimulus. This transcriptional memory state at Polycomb targets operates in cis; however, rather than relying solely on read-and-write propagation of histone modifications, the memory is also linked to the strength of activating inputs opposing Polycomb proteins, and therefore varies with the cellular context. Our data and computational simulations suggest a model whereby transcriptional memory arises from double-negative feedback between Polycomb-mediated silencing and active transcription. Transcriptional memory at Polycomb targets thus depends not only on histone modifications but also on the gene-regulatory network and underlying identity of a cell.
AB - Epigenetic inheritance of gene expression states enables a single genome to maintain distinct cellular identities. How histone modifications contribute to this process remains unclear. Using global chromatin perturbations and local, time-controlled modulation of transcription, we establish the existence of epigenetic memory of transcriptional activation for genes that can be silenced by the Polycomb group. This property emerges during cell differentiation and allows genes to be stably switched after a transient transcriptional stimulus. This transcriptional memory state at Polycomb targets operates in cis; however, rather than relying solely on read-and-write propagation of histone modifications, the memory is also linked to the strength of activating inputs opposing Polycomb proteins, and therefore varies with the cellular context. Our data and computational simulations suggest a model whereby transcriptional memory arises from double-negative feedback between Polycomb-mediated silencing and active transcription. Transcriptional memory at Polycomb targets thus depends not only on histone modifications but also on the gene-regulatory network and underlying identity of a cell.
U2 - 10.1038/s41588-021-00964-2
DO - 10.1038/s41588-021-00964-2
M3 - Journal article
C2 - 34782763
AN - SCOPUS:85119371224
VL - 53
SP - 1686
EP - 1697
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
ER -
ID: 285943324