Biology subjects

Sameith, K.

Publications and source records attributed to Sameith, K..

4 recordsLinked to original sources

bioRxiv2026

Nup153 regulates neuronal responsiveness through HDAC1-mediated epigenetic modulation

Neural activity-dependent gene regulation is central to the development of neural networks and neuronal plasticity. Induction of activity-dependent gene programs is equally important as repression of these programs, and both need to be balanced carefully. However, little is known about how repressive mechanisms modulate neuronal responsiveness across the genome before stimulation. Here, we identify nucleoporin-dependent regulation of neuronal responsiveness, in which Nup153 represses neuronal genes including activity-regulated genes (ARGs), in the basal state. By characterizing the genome-wide landscape of chromatin accessibility, histone modifications and Nup153 chromatin binding, we show that Nup153 bidirectionally regulates chromatin states through both basal activity-dependent and -independent mechanisms and influences associated genes. Mechanistically, Nup153 associates with HDAC1 to modulate histone acetylation and chromatin accessibility at target regulatory regions. Our data suggests Nup153 organizes chromatin states that regulate neuronal gene programs involved in maintaining neuronal responsiveness. TeaserNup153 primes neuronal responsiveness through multi-layered epigenetic regulation.

neuroscience↗

bioRxiv2024

Epigenome profiling identifies H3K27me3 regulation of extra-cellular matrix composition in human corticogenesis

Epigenetic mechanisms regulate gene expression programs during neurogenesis, but the extent of epigenetic remodelling during human cortical development remains unknown. Here, we characterize the epigenetic landscape of the human developing neocortex by leveraging Epi-CyTOF, a mass cytometry-based approach for the simultaneous single cell analysis of more than 30 epigenetic marks. We identify H3K27me3, deposited by Polycomb Repressive Complex 2 (PRC2), as the modification with the strongest cell type-specific enrichment. Inhibition of PRC2 in human cortical organoids resulted in a shift of neural progenitor cell (NPC) proliferation towards differentiation. Cell type- specific profiling of H3K27me3 not only identified neuronal differentiation genes in the human neocortex, but also extra-cellular matrix (ECM) genes. PRC2 inhibition resulted in increased production of the proteoglycan Syndecan 1. Overall, this study comprehensively characterizes the epigenetic state of specific neural cell types and highlights a novel role for H3K27me3 in regulating the ECM composition in the human developing neocortex.

developmental biology↗

bioRxiv2024

Differences in chromatin accessibility between renal cortex and inner medulla correlate with spatial differences in gene expression and are modulated by NFAT5 function

A spatial gene expression pattern between the cortex (CTX) and inner medulla (IM) of the kidney has been observed, but the underlying mechanisms are unclear. Understanding these mechanisms is essential for elucidating renal function. Using the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) we analyzed the open chromatin structures and the involvement of epigenetic mechanisms in mediating gene expression differences between the renal CTX and IM. We also examined the role of the nuclear factor of activated T cells 5 (NFAT5), a key regulator of hypertonicity. ATAC-seq analysis was performed on CTX and IM samples from both wild-type (WT) and NFAT5 knockout (KO) mice. This work demonstrates for the first time that these differences in gene expression between renal CTX and IM are associated with an epigenetic mechanism driven by chromatin accessibility, which is partially modulated by the nuclear factor of activated T-cells 5 (NFAT5) in mice. Furthermore, spatial localization and NFAT5-promoted chromatin accessibility correlate with differential gene expression and altered promoter binding motif enrichment in CTX and IM. This study provides new insights into the spatial and NFAT5-mediated regulation of chromatin accessibility and gene expression in CTX and IM. This work advances our understanding of kidney physiology by uncovering previously unknown epigenetic factors influencing gene expression and provides a new perspective on renal adaptive mechanisms. TRANSLATIONAL STATEMENTThe study reveals new insights into the spatial and epigenetic regulation of gene expression in the renal cortex (CTX) and inner medulla (IM) in the mouse kidney. We used the Assay for Transposase-Accessible Chromatin with High-Throughput Sequence Analysis (ATAC-seq) to identify a key role of NFAT5 in modulating chromatin accessibility and to uncover previously unknown epigenetic factors. This research enhances our understanding of renal physiology and has important implications for clinical care by providing insights into potential adaptive mechanisms in the kidney. These findings suggest future investigations targeting epigenetic signaling pathways for therapeutic intervention in renal diseases.

genomics↗

bioRxiv2017

Phenotype loss is associated with widespread divergence of the gene regulatory landscape in evolution

Detecting the genomic changes underlying phenotypic changes between species is a main goal of evolutionary biology and genomics. Evolutionary theory predicts that changes in cis-regulatory elements are important for morphological changes. Here, we combine genome sequencing and functional genomics with genome-wide comparative analyses to investigate the fate of regulatory elements in lineages that lost morphological traits. We first show that limb loss in snakes is associated with widespread divergence of limb regulatory elements. We next show that eye degeneration in subterranean mammals is associated with widespread divergence of eye regulatory elements. In both cases, sequence divergence results in an extensive loss of relevant transcription factor binding sites. Importantly, diverged regulatory elements are associated with key genes required for normal limb patterning or normal eye development and function, suggesting that regulatory divergence contributed to the loss of these phenotypes. Together, our results provide the first evidence that genome-wide decay of the phenotype-specific cis-regulatory landscape is a hallmark of lost morphological traits.

genomics↗