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Heterochromatic 3D genome organization is directed by HP1a- and H3K9-dependent and independent mechanisms.
- Source :
-
Molecular cell [Mol Cell] 2024 Jun 06; Vol. 84 (11), pp. 2017-2035.e6. Date of Electronic Publication: 2024 May 24. - Publication Year :
- 2024
-
Abstract
- Whether and how histone post-translational modifications and the proteins that bind them drive 3D genome organization remains unanswered. Here, we evaluate the contribution of H3K9-methylated constitutive heterochromatin to 3D genome organization in Drosophila tissues. We find that the predominant organizational feature of wild-type tissues is the segregation of euchromatic chromosome arms from heterochromatic pericentromeres. Reciprocal perturbation of HP1a⋅H3K9me binding, using a point mutation in the HP1a chromodomain or replacement of the replication-dependent histone H3 with H3 <superscript>K9R</superscript> mutant histones, revealed that HP1a binding to methylated H3K9 in constitutive heterochromatin is required to limit contact frequency between pericentromeres and chromosome arms and regulate the distance between arm and pericentromeric regions. Surprisingly, the self-association of pericentromeric regions is largely preserved despite the loss of H3K9 methylation and HP1a occupancy. Thus, the HP1a⋅H3K9 interaction contributes to but does not solely drive the segregation of euchromatin and heterochromatin inside the nucleus.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Methylation
Euchromatin metabolism
Euchromatin genetics
Centromere metabolism
Centromere genetics
Protein Binding
Genome, Insect
Chromosome Segregation
Protein Processing, Post-Translational
Heterochromatin metabolism
Heterochromatin genetics
Histones metabolism
Histones genetics
Chromosomal Proteins, Non-Histone metabolism
Chromosomal Proteins, Non-Histone genetics
Chromobox Protein Homolog 5
Drosophila Proteins metabolism
Drosophila Proteins genetics
Drosophila melanogaster genetics
Drosophila melanogaster metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 84
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 38795706
- Full Text :
- https://doi.org/10.1016/j.molcel.2024.05.002