Biology subjects

Kinney, J.

Publications and source records attributed to Kinney, J..

3 recordsLinked to original sources

bioRxiv2026

A developmental timer coordinates organism-wide microRNA transcription

The development of distinct tissues must be precisely coordinated to ensure that growth and cell fate transitions occur in the correct temporal order across the organism, yet the mechanisms that coordinate these timing events remain unclear. In Caenorhabditis elegans, stage-specific cell fate transitions are driven by pulsatile transcription of heterochronic microRNAs, but the source of these rhythms has been unknown. Here, we identify a developmental timer composed of the transcription factor MYRF-1 and the PERIOD-like repressor LIN-42 that operates in all somatic cells. MYRF-1 binds conserved regulatory elements upstream of heterochronic microRNA genes and drives synchronized, once-per-stage transcriptional pulses across tissues, while concurrently activating lin-42 expression. Newly synthesized LIN-42 directly associates with MYRF-1, limiting its nuclear residence and transcriptional activity to constrain the amplitude and duration of each transcriptional burst. This reciprocal transcriptional/translational feedback loop generates organism-wide, phase-locked microRNA expression, coupling tissue-specific development to organismal growth through a shared timing mechanism.

developmental biology↗

bioRxiv2023

Investigating Metabolic Trends in the Oral Cavity to Identify Novel Metabolites

The human oral microbiome typically contains over 700 different microbial species. These interactions between the microorganisms within this community can shape the microenvironment throughout the human body, as these interactions are paramount to maintaining oral and overall systemic health. Recent advances in technology, such as next-generation sequencing (NGS), have revealed the complexities of the oral microbiome, linking dysbiosis of the oral microbiome with several chronic ailments such as cardiovascular disease, diabetes, and inflammatory bowel disease. However, the role of microbial secondary metabolites in oral and systemic disease progression remains poorly understood. Here, we conducted a metabolomics study on the human salivary secondary metabolome during the induction of gingival inflammation (gingivitis), the precursor to periodontal disease. In this study, we sought to assess the changes in the oral secondary metabolome during disease progression by emulating dysbiosis of the oral microbiome through a twenty-one-day induction of gingivitis in twenty human participants. We identified secondary metabolites, cyclo(L-Tyr-L-Pro) with regulatory properties for quorum sensing and inflammatory marker secretion, indicating a specialized role for secondary metabolites in oral health maintenance. Surprisingly, we also uncovered a previously unknown metabolic lag that occurs during dysbiosis recovery of the oral cavity, which indicates a lingering presence of signaling molecules for pathogenic microbe proliferation or a total oral metabolome modification following microenvironmental stress in the oral cavity. This work represents a high-resolution metabolomic landscape for understanding oral health during gingivitis that opens new opportunities for combating progressive periodontal diseases and sepsis due to the translocation of oral microbes in the human body.

molecular biology↗

bioRxiv2020

The RSC complex remodels nucleosomes in transcribed coding sequences and promotes transcription in Saccharomyces cerevisiae

RSC (Remodels the Structure of Chromatin) is a conserved ATP-dependent chromatin remodeling complex that regulates many biological processes, including transcription by RNA polymerase II (Pol II). We report that RSC contributes to generation of accessible nucleosomes in transcribed coding sequences (CDSs). RSC MNase ChIP-seq data revealed that RSC-bound nucleosome fragments were very heterogenous (~80 bp to 180 bp) compared to a sharper profile displayed by the MNase inputs (140 bp to 160 bp), supporting the idea that RSC promotes accessibility of nucleosomal DNA. Notably, RSC binding to +1 nucleosomes and CDSs, but not with -1 nucleosomes, strongly correlated with Pol II occupancies, suggesting that RSC enrichment in CDSs is linked to transcription. We also observed that Pol II associates with nucleosomes throughout transcribed CDSs, and similar to RSC, Pol II-protected fragments were highly heterogenous, consistent with the idea that Pol II interacts with remodeled nucleosome in CDSs. This idea is supported by the observation that the genes harboring high-levels of RSC in their CDSs were the most strongly affected by ablating RSC function. We also find that rapid nuclear depletion of Sth1 decreases nucleosome accessibility and results in accumulation of Pol II in highly transcribed CDSs. This is consistent with a slower clearance of elongating Pol II in cells with reduced RSC function, and is distinct from the effect of RSC depletion on PIC assembly. Altogether, our data provide evidence in support of the role of RSC in promoting Pol II elongation, in addition to its role in regulating transcription initiation.

genomics↗