HP1a, Su(var)3-9, SETDB1 and POF stimulate or repress gene expression depending on genomic position, gene length and expression pattern in Drosophila melanogaster

Abstract

Heterochromatin protein 1a (HP1a) is a chromatin-associated protein important for the formation and maintenance of heterochromatin. In Drosophila, the two histone methyltransferases SETDB1 and Su(var)3-9 mediate H3K9 methylation marks that initiates the establishment and spreading of HP1a-enriched chromatin. Although HP1a is generally regarded as a factor that represses gene transcription, several reports have linked HP1a binding to active genes, and in some cases, it has been shown to stimulate transcriptional activity. To clarify the function of HP1a in transcription regulation and its association with Su(var)3-9, SETDB1 and the chromosome 4-specific protein POF, we conducted genome-wide expression studies and combined the results with available binding data in Drosophila melanogaster. The results suggest that HP1a, SETDB1 and Su(var)3-9 repress genes on chromosome 4, where non-ubiquitously expressed genes are preferentially targeted, and stimulate genes in pericentromeric regions. Further, we showed that on chromosome 4, Su(var)3-9, SETDB1 and HP1a target the same genes. In addition, we found that transposons are repressed by HP1a and Su(var)3-9 and that the binding level and expression effects of HP1a are affected by gene length. Our results indicate that genes have adapted to be properly expressed in their local chromatin environment.

Paternal Diet Defines Offspring Chromatin State and Intergenerational Obesity

“…We examined profiles from Su(var) 3-9 06/evo , SetDB1 10.1 , and HP1 04/05 mutant first-instar larvae (Lundberg et al, 2013) and Pc-and Pho-RNAi knockdown embryos (Goodliffe et al, 2007). Intriguingly, $70% overlap was observed between our significantly dysregulated IGMR genes and those responsive to H3K9-centric or polycomb insufficiency ( Figures 5F and 5G).…”

“…To test whether these signatures might directly contribute to metabolic reprogramming, we performed GSEA analysis of the Lundberg et al (2013) and Goodliffe et al (2007) data sets. Coordinate overlapping enrichment signatures were observed for key pathways of all five major IGMR clusters ( Figure 5M and Table S2), including most chromatin and primary energy modules.…”

“…(B) Volcano plot. (C and D) IGMR expression changes in sperm of high-relative to medium-sugar-fed fathers (C) for the five chromatin colors according toFilion et al (2010) and (D) for 200 most up-or downregulated genes from Su(var)3-9 06/evo mutants fromLundberg et al (2013).…”

Direct interrogation of the role of H3K9 in metazoan heterochromatin function

“…Because the endo-siRNA pathway is predominantly active in nongonadal somatic cells, we speculate that the absence of H3K9 disrupts this pathway. Previous studies have demonstrated that mutations in H3K9 methyltransferases and HP1 result in transposon activation (Brower-Toland et al 2009;Lundberg et al 2013). Increased piRNA levels could therefore be a response to this activation.…”

Targeting of Painting of fourth to roX1 and roX2 Proximal Sites Suggests Evolutionary Links Between Dosage Compensation and the Regulation of the fourth Chromosome in Drosophila melanogaster

“…The presence and degree of spreading differed between nuclei, and we typically saw 1-3 bands decorated by POF in both PoX1 and PoX2 . In addition to the two loci on the X-chromosome, we occasionally observed POF binding in parts of the 2L:31 region in both males and females (Figure 1) (Lundberg et al 2013). …”