Biology subjects

Balasooriya, G. I.

Publications and source records attributed to Balasooriya, G. I..

3 recordsLinked to original sources

bioRxiv2023

A sub-set of guanine- and cytosine-rich genes are actively transcribed at the nuclear Lamin B1 region

Chromatin organization in the mammalian cell nucleus plays a vital role in the regulation of gene expression. The lamina-associated domain at the inner nuclear membrane has been shown to harbor heterochromatin, while the nuclear interior has been shown to contain most of the euchromatin. Here, we show that a sub-set of actively transcribing genes, marked by RNA Pol II pSer2, are associated with Lamin B1 at the inner nuclear envelope in mouse embryonic stem cells (mESCs) and the number of genes proportionally increases upon in vitro differentiation of mESC to olfactory precursor cells. These nuclear periphery-associated actively transcribing genes primarily represent housekeeping genes, and their gene bodies are significantly enriched with guanine and cytosine compared to genes actively transcribed at the nuclear interior. We found the promoters of these genes to also be significantly enriched with guanine and to be predominantly regulated by zinc finger protein transcription factors. We provide evidence supporting the emerging notion that the Lamin B1 region is not solely transcriptionally silent.

cell biology↗

bioRxiv2023

Allele pairing at Sun1-enriched domains at the nuclear periphery via T1A3 tandem DNA repeats

Spatiotemporal gene regulation is fundamental to the biology of diploid cells. Therefore, effective communication between two alleles and their geometry in the nucleus is important. However, the mechanism that fine-tunes the expression from each of the two alleles of an autosome is enigmatic. By developing an allele-specific gene expression visualization system in living cells, we show that alleles of biallelically expressed Cth and Ttc4 genes are paired prior to acquiring monoallelic expression. We found that active alleles of monoallelic genes are preferentially localized at Sun1-enriched domains at the nuclear periphery. These peripherally localized euchromatic DNA loci harboring monoalleleic genes are enriched with adenine-thymidine-rich tandem repeats, which are bound by Hnrnpd, the "molecular wrench", to localize these loci in a Hi-C-defined A compartment within the B compartment. Our results demonstrate the biological significance of T1A3 tandem repeat sequences in genome organization and how the regulation of gene expression, at the level of individual alleles, relates to their spatial arrangement.

cell biology↗

bioRxiv2022

Autosomal monoallelic genes are differentially regulated based on parental origin

Each mammalian autosomal gene is represented by two alleles in diploid cells. Yet, no insights have been made in regard to allele-specific regulatory mechanisms of autosomes. Here we used allele-specific single cell transcriptomic analysis to elucidate the establishment of monoallelic gene expression in the cardiac lineage. We found that monoallelically expressed autosomal genes in mESCs and mouse blastocyst cells are differentially regulated based on the genetic background of the parental alleles. However, the genetic background of the allele does not affect the establishment of monoallelic genes in differentiated cardiomyocytes. Additionally, we observed epigenetic differences between deterministic and random autosomal monoallelic genes. Moreover, we also found a greater contribution of the maternal versus paternal allele to the development and homeostasis of cardiac tissue and in cardiac health, highlighting the importance of maternal influence in male cardiac tissue homeostasis. Our findings emphasize the significance of allele- specific insights into gene regulation in development, homeostasis and disease.

genetics↗