Biology subjects

Morris, K. J.

Publications and source records attributed to Morris, K. J..

2 recordsLinked to original sources

bioRxiv2025

Specialised super-enhancer networks in stem cells and neurons

Super-enhancers (SEs) are clusters of enhancers with high transcriptional activity that play essential roles in defining cell identity through regulation of nearby genes. SEs preferentially form multiway chromatin interactions with other SEs and highly transcribed regions in embryonic stem cells. However, the properties of the interacting SEs and their specific contributions to complex regulatory interactions in differentiated cell types remain poorly understood. Here, we compare the structural and functional properties of SEs between embryonic stem cells (ESCs) and dopaminergic neurons (DNs) by combining Genome Architecture Mapping (GAM), chromatin accessibility, histone modification, and transcriptome data. Most SEs are cell-type specific and establish extensive pairwise and multiway chromatin interactions with other SEs and genes with cell-type specific expression. SE interactions span megabase genomic distances and frequently connect distant topologically associating domains. By applying network centrality analyses, we detected SEs with different hierarchical importance. Highest network centrality SEs contain binding motifs for cell-type specific transcription factors, and are candidate regulatory hubs. The functional heterogeneity of SEs is also highlighted by their organisation into modular sub-networks that differ in structure and spatial scale between ESCs and DNs, with more specific and strongly connected SE modules in post-mitotic neurons. Our results uncover both the high complexity and specificity of SE-based 3D regulatory networks and provide a resource for prioritizing SEs with potential roles in transcriptional regulation and disease.

genomics↗

bioRxiv2020

The Polyadenosine RNA Binding Protein ZC3H14 is Required in Mice for Proper Dendritic Spine Density

ZC3H14 (Zinc finger CysCysCysHis domain-containing protein 14), an evolutionarily conserved member of a class of tandem zinc finger (CCCH) polyadenosine (polyA) RNA binding proteins, is associated with a form of heritable, nonsyndromic autosomal recessive intellectual disability. Previous studies of a loss of function mouse model, Zc3h14{Delta}ex13/{Delta}ex13, provide evidence that ZC3H14 is essential for proper brain function, specifically for working memory. To expand on these findings, we analyzed the dendritic spines of hippocampal neurons from Zc3h14{Delta}ex13/{Delta}ex13 mice. These studies reveal that loss of ZC3H14 does not affect dendritic spine density in either CA1 pyramidal neurons or dentate gyrus granule cells in the hippocampus. However, overexpression of ZC3H14 in cultured hippocampal neurons increases the overall density of spines. We next performed biochemical analyses of synaptosomes prepared from whole wild-type and Zc3h14{Delta}ex13/{Delta}ex13 mouse brains to determine if there are changes in steady state levels of postsynaptic proteins upon the loss of ZC3H14. We found that ZC3H14 is present within synaptosomes and that a crucial postsynaptic protein, CaMKII, is significantly increased in these synaptosomal fractions upon loss of ZC3H14. Together, these results demonstrate that ZC3H14 localizes to synapses, that its levels influence dendritic spine morphology, and that its loss dysregulates synaptic CaMKII levels, suggesting a potential role for ZC3H14 in synaptic function and plasticity.

neuroscience↗