Shining Light on the Dark Side of the Genome

Abstract

Heterochromatin has historically been considered the dark side of the genome. In part, this reputation derives from its concentration near centromeres and telomeres, regions of the genome repressive to nuclear functions such as DNA replication and transcription. The repetitive nature of heterochromatic DNA has only added to its “darkness”, as sequencing of these DNA regions has been only recently achieved. Despite such obstacles, research on heterochromatin blossomed over the past decades. Success in this area benefitted from efforts of Sergio Pimpinelli and colleagues who made landmark discoveries and promoted the growth of an international community of researchers. They discovered complexities of heterochromatin, demonstrating that a key component, Heterochromatin Protein 1a (HP1a), uses multiple mechanisms to associate with chromosomes and has positive and negative effects on gene expression, depending on the chromosome context. In addition, they updated the work of Carl Waddington using molecular tools that revealed how environmental stress promotes genome change due to transposable element movement. Collectively, their research and that of many others in the field have shined a bright light on the dark side of the genome and helped reveal many mysteries of heterochromatin.

Satellite DNAs—From Localized to Highly Dispersed Genome Components

“…The DNA sequences dominantly present in constitutive heterochromatin are repetitive, mostly satDNAs. Complex interactions of satDNAs and their transcripts with specific protein components, in combination with unique epigenetic modifications, define specificities in heterochromatin structure and function, such as tightly packed nucleosomes, generally repressive effects on gene expression or the role in maintening the cohesion of sister chromatids [ 23 , 163 , 164 ].…”

Using the genome to correct the ion transport defect in cystic fibrosis

“…Notwithstanding, these approaches somehow fail to meet their expectations, as they commonly just deliver long lists of ‘candidate’ gene products or pathways that are putatively associated with the respective disease. For many of these genes (and especially for other ‘darker’ regions of the genome) there no functional information, even less their relevance or direct relationship with the pathological conditions, has been established (Oprea, 2019; Wallrath et al., 2022; Wright et al., 2022). As they have been recently reviewed elsewhere (Ideozu et al., 2019; Liessi et al., 2020; Shi et al., 2019; Strub & McCray, 2020) they are not reviewed in detail here.…”

SafeguardingDrosophilafemale germ cell identity depends on an H3K9me3 mini domain guided by a ZAD zinc finger protein

“…The repressive H3K9me3 histone modification has well-characterized roles in constitutive heterochromatin formation, repression of satellite repeats, and repression of transposable elements (TEs) (Janssen et al, 2018; Marsano and Dimitri, 2022; Wallrath et al, 2022). These studies identified two mechanisms of H3K9me3 recruitment.…”