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Doni Jayavelu, N.

Publications and source records attributed to Doni Jayavelu, N..

3 recordsLinked to original sources
bioRxiv2019

Single-cell analysis of Non-CpG methylation dynamics and gene expression in human oocyte maturation

Oocyte maturation is a coordinated process that is tightly linked to reproductive potential. A better understanding of gene regulation during human oocyte maturation will not only answer an important question in biology, but also facilitate the development of in vitro maturation technology as a fertility treatment. We generated single-cell transcriptome and use previously published single-cell methylome data from human oocytes at different maturation stages to investigate how genes are regulated during oocyte maturation, focusing on the potential regulatory role of non-CG methylation. DNMT3B, a gene encoding a key non-CG methylation enzyme, is one of the 1000 genes upregulated in mature oocytes, which may be at least partially responsible for the increased non-CG methylation as oocytes mature. Non-CG differentially methylated regions (DMRs) between mature and immature oocytes have multiple binding motifs for transcription factors, some of which bind with DNMT3B and may be important regulators of oocyte maturation through non-CG methylation. Over 98% of non-CG DMRs locate in transposable elements, and these DMRs are correlated with expression changes of the nearby genes. Taken together, this data indicates that global non-CG hypermethylation during oocyte maturation may play an active role in gene expression regulation, potentially through the interaction with transcription factors.

developmental biology↗
bioRxiv2018

An atlas of silencer elements for the human and mouse genomes

The study of gene regulation is dominated by a focus on the control of gene activation or controlling an increase in the level of expression. Just as critical is the process of gene repression or silencing. Chromatin signatures have allowed for the global mapping of enhancer cis-regulatory elements, however, the identification of silencer elements by computational or experimental approaches in a genome-wide manner are lacking. We present a simple but powerful computational approach to identify putative silencers genome-wide. We used a series of consortia data to predict silencers in over 100 human and mouse cell or tissue types. We performed several analyses to determine if these elements exhibited characteristics expected of a silencers. Motif enrichment analyses on putative silencers determined that motifs belonging to known transcriptional repressors are enriched, as well as overlapping known transcription repressor binding sites. Leveraging promoter capture HiC data from several human and mouse cell types, we found that over 50% of putative silencer elements are interacting with gene promoters having very low to no expression. Next, to validate our silencer predictions, we quantified silencer activity using massively parallel reporter assays (MPRAs) on 7500 selected elements in K562 cells. We trained a support vector machine model classifier on MPRA data and used it to refine potential silencers in other cell types. We also show that similar to enhancer elements, silencer elements are enriched in disease-associated variants. Our results suggest a general strategy for genome-wide identification and characterization of silencer elements.

genomics↗
bioRxiv2017

Epigenomic and 3D genome architecture in naïve and primed human embryonic stem cell states

During mammalian embryogenesis changes in morphology and gene expression are concurrent with epigenomic reprogramming. Using human embryonic stem cells representing the pre-implantation blastocyst (naive) and post-implantation epiblast (primed), our data demonstrate that a substantial portion of known human enhancers are pre-marked by H3K4me1 in naive cells, providing an enhanced open chromatin state in naive pluripotency. The naive enhancer repertoire occupies nine percent of the genome, three times that of primed cells, and can exist in broad chromatin domains over fifty kilobases. Enhancer chromatin states are largely poised. Seventy-seven percent of naive enhancers are decommissioned in a stepwise manner as cells become primed. While primed topological associated domains are unaltered upon differentiation, naive domains expand across primed boundaries, impacting three dimensional genome architecture. Differential topological associated domain edges coincide with naive H3K4me1 enrichment. Our results suggest that naive-derived cells have a chromatin landscape reflective of early embryogenesis.

developmental biology↗