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Polycomb-lamina antagonism partitions heterochromatin at the nuclear periphery
by
Wagen, Corin C.
, Siegenfeld, Allison P.
, Johnstone, Sarah E.
, Liau, Brian B.
, Roh, Heejin
, Lue, Nicholas Z.
, Zhou, Eric
, Aryee, Martin J.
, Roseman, Shelby A.
in
13/106
/ 13/51
/ 38/22
/ 38/23
/ 38/91
/ 45/15
/ 45/77
/ 631/1647/2217
/ 631/208/177
/ 631/80/386/1700
/ Chromatin
/ Chromosomes
/ Compartments
/ Conformation
/ Deoxyribonucleic acid
/ DNA
/ DNA methylation
/ Epigenetics
/ Genomes
/ Heterochromatin
/ Humanities and Social Sciences
/ Lime
/ multidisciplinary
/ Polycomb group proteins
/ Position measurement
/ Science
/ Science (multidisciplinary)
2022
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Polycomb-lamina antagonism partitions heterochromatin at the nuclear periphery
by
Wagen, Corin C.
, Siegenfeld, Allison P.
, Johnstone, Sarah E.
, Liau, Brian B.
, Roh, Heejin
, Lue, Nicholas Z.
, Zhou, Eric
, Aryee, Martin J.
, Roseman, Shelby A.
in
13/106
/ 13/51
/ 38/22
/ 38/23
/ 38/91
/ 45/15
/ 45/77
/ 631/1647/2217
/ 631/208/177
/ 631/80/386/1700
/ Chromatin
/ Chromosomes
/ Compartments
/ Conformation
/ Deoxyribonucleic acid
/ DNA
/ DNA methylation
/ Epigenetics
/ Genomes
/ Heterochromatin
/ Humanities and Social Sciences
/ Lime
/ multidisciplinary
/ Polycomb group proteins
/ Position measurement
/ Science
/ Science (multidisciplinary)
2022
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Polycomb-lamina antagonism partitions heterochromatin at the nuclear periphery
by
Wagen, Corin C.
, Siegenfeld, Allison P.
, Johnstone, Sarah E.
, Liau, Brian B.
, Roh, Heejin
, Lue, Nicholas Z.
, Zhou, Eric
, Aryee, Martin J.
, Roseman, Shelby A.
in
13/106
/ 13/51
/ 38/22
/ 38/23
/ 38/91
/ 45/15
/ 45/77
/ 631/1647/2217
/ 631/208/177
/ 631/80/386/1700
/ Chromatin
/ Chromosomes
/ Compartments
/ Conformation
/ Deoxyribonucleic acid
/ DNA
/ DNA methylation
/ Epigenetics
/ Genomes
/ Heterochromatin
/ Humanities and Social Sciences
/ Lime
/ multidisciplinary
/ Polycomb group proteins
/ Position measurement
/ Science
/ Science (multidisciplinary)
2022
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Polycomb-lamina antagonism partitions heterochromatin at the nuclear periphery
Journal Article
Polycomb-lamina antagonism partitions heterochromatin at the nuclear periphery
2022
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Overview
The genome can be divided into two spatially segregated compartments, A and B, which partition active and inactive chromatin states. While constitutive heterochromatin is predominantly located within the B compartment near the nuclear lamina, facultative heterochromatin marked by H3K27me3 spans both compartments. How epigenetic modifications, compartmentalization, and lamina association collectively maintain heterochromatin architecture remains unclear. Here we develop Lamina-Inducible Methylation and Hi-C (LIMe-Hi-C) to jointly measure chromosome conformation, DNA methylation, and lamina positioning. Through LIMe-Hi-C, we identify topologically distinct sub-compartments with high levels of H3K27me3 and differing degrees of lamina association. Inhibition of Polycomb repressive complex 2 (PRC2) reveals that H3K27me3 is essential for sub-compartment segregation. Unexpectedly, PRC2 inhibition promotes lamina association and constitutive heterochromatin spreading into H3K27me3-marked B sub-compartment regions. Consistent with this repositioning, genes originally marked with H3K27me3 in the B compartment, but not the A compartment, remain largely repressed, suggesting that constitutive heterochromatin spreading can compensate for H3K27me3 loss at a transcriptional level. These findings demonstrate that Polycomb sub-compartments and their antagonism with lamina association are fundamental features of genome structure. More broadly, by jointly measuring nuclear position and Hi-C contacts, our study demonstrates how compartmentalization and lamina association represent distinct but interdependent modes of heterochromatin regulation.
Here the authors developed ‘Lamina-Inducible Methylation and Hi-C’ (LIMe-Hi-C) to simultaneously measure chromosome conformation, DNA methylation, and nuclear lamina positioning. Application of the method revealed dynamic changes upon PRC2 inhibition and an essential function of H3K27me3 in regulating sub-compartments and lamina association.
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