In eukaryotic cells, heterochromatin is typically composed of tandem DNA repeats and plays crucial roles in gene expression and genome stability. It has been reported that silencing at individual units within tandem heterochromatin repeats exhibits a position‐dependent variation. However, how the heterochromatin is organized at an individual repeat level remains poorly understood. Using a novel genetic approach, our recent study identified a conserved protein Rex1BD required for position‐dependent silencing within heterochromatin repeats. We further revealed that Rex1BD interacts with the 14‐3‐3 protein to regulate heterochromatin silencing by linking RNAi and HDAC pathways. In this review, we discuss how Rex1BD and the 14‐3‐3 protein coordinate to modulate heterochromatin organization at the individual repeat level, and comment on the biological significance of the position‐dependent effect in heterochromatin repeats. We also identify the knowledge gaps that still need to be unveiled in the field.
This content will become publicly available on December 12, 2024
Tandem DNA repeats are often organized into heterochromatin that is crucial for genome organization and stability. Recent studies revealed that individual repeats within tandem DNA repeats can behave very differently. How DNA repeats are assembled into distinct heterochromatin structures remains poorly understood. Here, we developed a genome-wide genetic screen using a reporter gene at different units in a repeat array. This screen led to identification of a conserved protein Rex1BD required for heterochromatin silencing. Our structural analysis revealed that Rex1BD forms a four-helix bundle structure with a distinct charged electrostatic surface. Mechanistically, Rex1BD facilitates the recruitment of Clr6 histone deacetylase (HDAC) by interacting with histones. Interestingly, Rex1BD also interacts with the 14-3-3 protein Rad25, which is responsible for recruiting the RITS (RNA-induced transcriptional silencing) complex to DNA repeats. Our results suggest that coordinated action of Rex1BD and Rad25 mediates formation of distinct heterochromatin structure at DNA repeats via linking RNAi and HDAC pathways.
more » « less- Award ID(s):
- 1934628
- NSF-PAR ID:
- 10530597
- Publisher / Repository:
- National Academy of Sciences
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 120
- Issue:
- 50
- ISSN:
- 0027-8424
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Across eukaryotes, gene regulation is manifested via chromatin states roughly distinguished as heterochromatin and euchromatin. The establishment, maintenance, and modulation of the chromatin states is mediated using several factors including chromatin modifiers. However, factors that avoid the intrusion of silencing signals into protein-coding genes are poorly understood. Here we show that a plant specific paralog of RNA polymerase (Pol) II, named Pol IV, is involved in avoidance of facultative heterochromatic marks in protein-coding genes, in addition to its well-established functions in silencing repeats and transposons. In its absence, H3K27 trimethylation (me3) mark intruded the protein-coding genes, more profoundly in genes embedded with repeats. In a subset of genes, spurious transcriptional activity resulted in small(s) RNA production, leading to post-transcriptional gene silencing. We show that such effects are significantly pronounced in rice, a plant with a larger genome with distributed heterochromatin compared with
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