A function of Spalt proteins in heterochromatin organization and maintenance of genomic DNA integrity

TL;DR

This paper shows that Spalt proteins in fruit flies help maintain genomic stability by organizing heterochromatin and preventing DNA damage.

Contribution

The study reveals that Spalt proteins have a dual role in gene silencing and heterochromatin maintenance in Drosophila.

Findings

Loss of Spalt function leads to DNA damage and altered chromatin accessibility.

Spalt proteins are linked to transposable element misexpression and chromosomal localization changes.

Spalt contributes to heterochromatin formation and global gene silencing.

Abstract

The conserved Spalt proteins regulate gene expression and cell fate choices during multicellular development, generally acting as transcriptional repressors in different gene regulatory networks. In addition to their roles as DNA sequence-specific transcription factors, Spalt proteins show a consistent localization to heterochromatic regions. Vertebrate Spalt-like proteins can act through the nucleosome remodeling and deacetylase complex to promote closing of open chromatin domains, but their activities also rely on interactions with DNA methyltransferases or with the lysine-specific histone demethylase LSD1, suggesting that they participate in multiple regulatory mechanisms. Here, we describe several consequences of loss of Spalt function in Drosophila cells, including changes in chromatin accessibility, generation of DNA damage, alterations in the localization of chromosomes within the nucleus in the salivary glands and misexpression of transposable elements. We suggest that these effects are related to roles of Spalt proteins in the regulation of heterochromatin formation and chromatin organization. We propose that Drosophila Spalt proteins have two complementary functions, acting as sequence-specific transcriptional repressors on specific target genes and regulating more global gene silencing through the generation or maintenance of heterochromatic domains.

Summary: The Drosophila Spalt proteins regulate gene silencing through the maintenance of heterochromatic domains. Loss of Spalt alters chromatin accessibility, causes misexpression of transposable elements and generates DNA damage and alterations in the localization of chromosomes within the nucleus.

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