Journal
EMBO REPORTS
Volume 23, Issue 12, Pages -Publisher
WILEY
DOI: 10.15252/embr.202254720
Keywords
Drosophila; gene regulation; heterochromatin proteins; insulator proteins; topological associated domains (TADs)
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Funding
- Legacy Heritage Bio-Medical Program of the Israel Science Foundation [839/10]
- Israel Science Foundation [575/17]
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This study finds that ROW protein interacts with BEAF-32, HP1b, and HP1c at the boundaries of TAD, leading to the regulation of long-range transcription of target genes.
Insulator proteins located at the boundaries of topological associated domains (TAD) are involved in higher-order chromatin organization and transcription regulation. However, it is still not clear how long-range contacts contribute to transcriptional regulation. Here, we show that relative-of-WOC (ROW) is essential for the long-range transcription regulation mediated by the boundary element-associated factor of 32kD (BEAF-32). We find that ROW physically interacts with heterochromatin proteins (HP1b and HP1c) and the insulator protein (BEAF-32). These proteins interact at TAD boundaries where ROW, through its AT-hook motifs, binds AT-rich sequences flanked by BEAF-32-binding sites and motifs. Knockdown of row downregulates genes that are long-range targets of BEAF-32 and bound indirectly by ROW (without binding motif). Analyses of high-throughput chromosome conformation capture (Hi-C) data reveal long-range interactions between promoters of housekeeping genes bound directly by ROW and promoters of developmental genes bound indirectly by ROW. Thus, our results show cooperation between BEAF-32 and the ROW complex, including HP1 proteins, to regulate the transcription of developmental and inducible genes through long-range interactions.
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