A composite DNA element that functions as a maintainer required for epigenetic inheritance of heterochromatin

Xiaoyi Wang; Joao A Paulo; Xue Li; Haining Zhou; Juntao Yu; Steven P Gygi; Danesh Moazed

doi:10.1016/j.molcel.2021.07.017

A composite DNA element that functions as a maintainer required for epigenetic inheritance of heterochromatin

Mol Cell. 2021 Oct 7;81(19):3979-3991.e4. doi: 10.1016/j.molcel.2021.07.017. Epub 2021 Aug 9.

Authors

Xiaoyi Wang¹, Joao A Paulo², Xue Li³, Haining Zhou¹, Juntao Yu¹, Steven P Gygi², Danesh Moazed⁴

Affiliations

¹ Howard Hughes Medical Institute, Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
² Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
³ Bioinformatics and Integrative Biology Program, University of Massachusetts Medical School, Worcester, MA, USA.
⁴ Howard Hughes Medical Institute, Department of Cell Biology, Harvard Medical School, Boston, MA, USA. Electronic address: danesh@hms.harvard.edu.

Abstract

Epigenetic inheritance of heterochromatin requires DNA-sequence-independent propagation mechanisms, coupling to RNAi, or input from DNA sequence, but how DNA contributes to inheritance is not understood. Here, we identify a DNA element (termed "maintainer") that is sufficient for epigenetic inheritance of pre-existing histone H3 lysine 9 methylation (H3K9me) and heterochromatin in Schizosaccharomyces pombe but cannot establish de novo gene silencing in wild-type cells. This maintainer is a composite DNA element with binding sites for the Atf1/Pcr1 and Deb1 transcription factors and the origin recognition complex (ORC), located within a 130-bp region, and can be converted to a silencer in cells with lower rates of H3K9me turnover, suggesting that it participates in recruiting the H3K9 methyltransferase Clr4/Suv39h. These results suggest that, in the absence of RNAi, histone H3K9me is only heritable when it can collaborate with maintainer-associated DNA-binding proteins that help recruit the enzyme responsible for its epigenetic deposition.

Keywords: Atf1; Clr4; Deb1; H3K9me; ORC; Pcr1; Suv39h; epigenetic inheritance; heterochromatin; maintainer.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Activating Transcription Factors / genetics
Activating Transcription Factors / metabolism
Adenosine Triphosphatases / genetics
Adenosine Triphosphatases / metabolism
Binding Sites
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism
Chromatin Assembly and Disassembly*
DNA Methylation*
DNA, Fungal / genetics*
DNA, Fungal / metabolism
Epigenesis, Genetic
Gene Expression Regulation, Fungal
Heredity*
Heterochromatin / genetics*
Heterochromatin / metabolism
Histone-Lysine N-Methyltransferase / genetics
Histone-Lysine N-Methyltransferase / metabolism
Histones / genetics
Histones / metabolism
Origin Recognition Complex / genetics
Origin Recognition Complex / metabolism
Proteins / genetics
Proteins / metabolism
RNA Interference
Regulatory Sequences, Nucleic Acid*
Schizosaccharomyces / genetics*
Schizosaccharomyces / metabolism
Schizosaccharomyces pombe Proteins / genetics
Schizosaccharomyces pombe Proteins / metabolism

Substances

Activating Transcription Factors
Cell Cycle Proteins
DNA, Fungal
Heterochromatin
Histones
Origin Recognition Complex
Pcr1 protein, S pombe
Proteins
Schizosaccharomyces pombe Proteins
Histone-Lysine N-Methyltransferase
clr4 protein, S pombe
alcohol O-acetyltransferase
Adenosine Triphosphatases
Rdp1 protein, S pombe

Abstract

Publication types

MeSH terms

Substances

Grants and funding