H3K9me selectively blocks transcription factor activity and ensures differentiated tissue integrity

TY - JOUR

T1 - H3K9me selectively blocks transcription factor activity and ensures differentiated tissue integrity

AU - Methot, Stephen P

AU - Padeken, Jan

AU - Brancati, Giovanna

AU - Zeller, Peter

AU - Delaney, Colin E

AU - Gaidatzis, Dimos

AU - Kohler, Hubertus

AU - van Oudenaarden, Alexander

AU - Großhans, Helge

AU - Gasser, Susan M

N1 - © 2021. The Author(s).

PY - 2021/11

Y1 - 2021/11

N2 - The developmental role of histone H3K9 methylation (H3K9me), which typifies heterochromatin, remains unclear. In Caenorhabditis elegans, loss of H3K9me leads to a highly divergent upregulation of genes with tissue and developmental-stage specificity. During development H3K9me is lost from differentiated cell type-specific genes and gained at genes expressed in earlier developmental stages or other tissues. The continuous deposition of H3K9me2 by the SETDB1 homolog MET-2 after terminal differentiation is necessary to maintain repression. In differentiated tissues, H3K9me ensures silencing by restricting the activity of a defined set of transcription factors at promoters and enhancers. Increased chromatin accessibility following the loss of H3K9me is neither sufficient nor necessary to drive transcription. Increased ATAC-seq signal and gene expression correlate at a subset of loci positioned away from the nuclear envelope, while derepressed genes at the nuclear periphery remain poorly accessible despite being transcribed. In conclusion, H3K9me deposition can confer tissue-specific gene expression and maintain the integrity of terminally differentiated muscle by restricting transcription factor activity.

AB - The developmental role of histone H3K9 methylation (H3K9me), which typifies heterochromatin, remains unclear. In Caenorhabditis elegans, loss of H3K9me leads to a highly divergent upregulation of genes with tissue and developmental-stage specificity. During development H3K9me is lost from differentiated cell type-specific genes and gained at genes expressed in earlier developmental stages or other tissues. The continuous deposition of H3K9me2 by the SETDB1 homolog MET-2 after terminal differentiation is necessary to maintain repression. In differentiated tissues, H3K9me ensures silencing by restricting the activity of a defined set of transcription factors at promoters and enhancers. Increased chromatin accessibility following the loss of H3K9me is neither sufficient nor necessary to drive transcription. Increased ATAC-seq signal and gene expression correlate at a subset of loci positioned away from the nuclear envelope, while derepressed genes at the nuclear periphery remain poorly accessible despite being transcribed. In conclusion, H3K9me deposition can confer tissue-specific gene expression and maintain the integrity of terminally differentiated muscle by restricting transcription factor activity.

U2 - 10.1038/s41556-021-00776-w

DO - 10.1038/s41556-021-00776-w

M3 - Article

C2 - 34737442

SN - 1465-7392

VL - 23

SP - 1163

EP - 1175

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 11

ER -