Induction of H3K9me3 and DNA methylation by tethered heterochromatin factors in Neurospora crassa

Functionally different chromatin domains display distinct chemical marks. Constitutive heterochromatin is commonly associated with trimethylation of lysine 9 on histone H3 (H3K9me3), hypoacetylated histones, and DNA methylation, but the contributions of and interplay among these features are not ful...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2017-11, Vol.114 (45), p.E9598-E9607
Main Authors: Gessaman, Jordan D., Selker, Eric U.
Format: Article
Language:English
Subjects:
Biological Sciences
Catalysis
Catalytic activity
Chromatin
Deacetylation
Deoxyribonucleic acid
DNA
DNA methylation
DNA methyltransferase
Gene silencing
Genes
Heterochromatin
Heterochromatin protein 1
Histone deacetylase
Histone H3
Histones
In vivo methods and tests
Localization
Lysine
Mold
Neurospora
Neurospora crassa
PNAS Plus
Proteins
Recruitment
Regulatory mechanisms (biology)
Tethering
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Functionally different chromatin domains display distinct chemical marks. Constitutive heterochromatin is commonly associated with trimethylation of lysine 9 on histone H3 (H3K9me3), hypoacetylated histones, and DNA methylation, but the contributions of and interplay among these features are not fully understood. To dissect the establishment of heterochromatin, we investigated the relationships among these features using an in vivo tethering system in Neurospora crassa. Artificial recruitment of the H3K9 methyltransferase DIM-5 (defective in methylation-5) induced H3K9me3 and DNA methylation at a normally active, euchromatic locus but did not bypass the requirement of DIM-7, previously implicated in the localization of DIM-5, indicating additional DIM-7 functionality. Tethered heterochromatin protein 1 (HP1) induced H3K9me3, DNA methylation, and gene silencing. The induced heterochromatin required histone deacetylase 1 (HDA-1), with an intact catalytic domain, but HDA-1 was not essential for de novo heterochromatin formation at native heterochromatic regions. Silencing did not require H3K9me3 or DNA methylation. However, DNA methylation contributed to establishment of H3K9me3 induced by tethered HP1. Our analyses also revealed evidence of regulatory mechanisms, dependent on HDA-1 and DIM-5, to control the localization and catalytic activity of the DNA methyltransferase DIM-2. Our study clarifies the interrelationships among canonical aspects of heterochromatin and supports a central role of HDA-1–mediated histone deacetylation in heterochromatin spreading and gene silencing.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1715049114