Heterochromatin Protein 1 (HP1a) Positively Regulates Euchromatic Gene Expression through RNA Transcript Association and Interaction with hnRNPs in Drosophila

Abstract

Heterochromatin Protein 1 (HP1a) is a well-known conserved protein involved in heterochromatin formation and gene silencing in different species including humans. A general model has been proposed for heterochromatin formation and epigenetic gene silencing in different species that implies an essential role for HP1a. According to the model, histone methyltransferase enzymes (HMTases) methylate the histone H3 at lysine 9 (H3K9me), creating selective binding sites for itself and the chromodomain of HP1a. This complex is thought to form a higher order chromatin state that represses gene activity. It has also been found that HP1a plays a role in telomere capping. Surprisingly, recent studies have shown that HP1a is present at many euchromatic sites along polytene chromosomes of Drosophila melanogaster, including the developmental and heat-shock-induced puffs, and that this protein can be removed from these sites by in vivo RNase treatment, thus suggesting an association of HP1a with the transcripts of many active genes. To test this suggestion, we performed an extensive screening by RIP-chip assay (RNA–immunoprecipitation on microarrays), and we found that HP1a is associated with transcripts of more than one hundred euchromatic genes. An expression analysis in HP1a mutants shows that HP1a is required for positive regulation of these genes. Cytogenetic and molecular assays show that HP1a also interacts with the well known proteins DDP1, HRB87F, and PEP, which belong to different classes of heterogeneous nuclear ribonucleoproteins (hnRNPs) involved in RNA processing. Surprisingly, we found that all these hnRNP proteins also bind heterochromatin and are dominant suppressors of position effect variegation. Together, our data show novel and unexpected functions for HP1a and hnRNPs proteins. All these proteins are in fact involved both in RNA transcript processing and in heterochromatin formation. This suggests that, in general, similar epigenetic mechanisms have a significant role on both RNA and heterochromatin metabolisms.

Heterochromatin remodeling by CDK12 contributes to learning in Drosophila

“…The first possibility is that HP1 may be relocated in the nucleus. HP1 is also found in the nucleoplasmic fraction (27), and its association with chromatin is dynamic (28). After CDK12 depletion, there may be more HP1 becoming associated with chromatin from the nucleoplasm.…”

MRG15 is required for pre-mRNA splicing and spermatogenesis

“…In fact, there are several complexes that include chromatin binding proteins (which recognize other histone modifications) and a splicing factor, such as H3K9me3/HP1a/hnRNPs, H3K4me3/CHD1/U2 snRNP, or acetylated H3/GCN5/U2 snRNP (5,(48)(49)(50)(51). Splicing regulation via an MRG15-PTBP2 complex may also be physiologically relevant to the brain, because PTBP2 expression is restricted to testis and brain, and MRG15 is ubiquitously expressed (52)(53)(54).…”

Sex-switching of theDrosophilabrain by two antagonistic chromatin factors

“…29 In Drosophila, HP1a upregulates the expression of some euchromatic genes through the association with heterogeneous nuclear ribonucleoproteins and RNA transcripts. 30 Similarly, it was reported that the association of HP1a with chromosomes leads to the expression of several HP1a target genes in euchromatin. 31,32 These findings are in concert with our idea that HDAC1, and perhaps HP1a also, in the Fru-protein complex not only silence but also activate target genes, depending on the developmental context, contributing to either the masculinization or demasculinization of fru-expressing neurons.…”