Transcriptional Activation of Mouse Major Satellite Regions during Neuronal Differentiation

Abstract

ABSTRACT. Recent studies have revealed various biological functions for repetitive sequences, which make up about half of the human genome. One such sequence, major satellites, which are tandem repetitive sequences adjacent to the centromere, have been shown to be a kinetochore component that plays a role in the formation and function of the pericentric heterochromatin necessary for mitosis. However, it is unknown whether these regions also play a role in post-mitotic cells. Here, we show that, during neuronal differentiation, the heterochromatin domains that include major satellite regions become both enriched with the active histone modification lysine-4 trimethylation of histone H3, and more sensitive to nuclease, both of which suggest increased activation of this area. Further supporting this notion, we also found that transcription from major satellite regions is significantly increased during neuronal differentiation both in vitro and in vivo. These results together suggest that the structural and transcriptional state of major satellite regions changes dramatically during neuronal differentiation, implying that this region might play a role in differentiating neurons.

Loss of Tau protein affects the structure, transcription and repair of neuronal pericentromeric heterochromatin

“…In murine and human cells, these transcripts are of varying lengths and can exist in both orientations with the sense and antisense RNAs not necessarily present in equal amounts, which suggests different regulatory mechanism for each one of the two different transcripts18323334. Transcription of PCH RNAs has been shown to vary during development2435, neuronal differentiation36, cell cycle37, in response to stress3839 and in tumour cells33. However, little is known concerning the regulation of their transcriptional rate.…”

Regulation of Chromatin Structure During Neural Development

“…For example, the number and shape of chromocenters – heterochromatin foci strongly stained with DNA-intercalating dyes – change during neuronal differentiation (Billia et al, 1992; Solovei et al, 2004, 2009; Clowney et al, 2012; Le Gros et al, 2016). Likewise, an increase in the deposition of the active histone mark H3K4me3 (trimethylated lysine-4 of histone H3) at chromocenters, accompanied by an increase in transcription of major satellites, is also observed during neuronal differentiation in the neocortex (Kishi et al, 2012b). Recent examinations of chromatin accessibility by the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), DNase-seq, and formaldehyde-assisted isolation of regulatory elements (FAIRE)-seq have revealed progressive changes in chromatin openness during neuronal differentiation processes (Frank et al, 2015; Thakurela et al, 2015; de la Torre-Ubieta et al, 2018; Preissl et al, 2018), which would link chromatin accessibility to the genome architecture associated with these processes.…”

MeCP2 and Major Satellite Forward RNA Cooperate for Pericentric Heterochromatin Organization

“…However, their biological significance remains unclear. MajSat RNA levels increase during neuronal differentiation in the developing mouse brain ( Kishi et al., 2012 ). Also, they participate in the recruitment to PCH of scaffold attachment factor B (SAFB) ( Huo et al., 2020 ) and suppressor of variegation 3-9 homolog (Suv39h), the enzyme responsible for trimethylation of H3K9 ( Velazquez Camacho et al., 2017 ), and they have roles in chromocenter condensation during myogenic differentiation ( Park et al., 2018 ).…”