Biology subjects

Feit, L.

Publications and source records attributed to Feit, L..

3 recordsLinked to original sources

bioRxiv2026

GH1-HMGA proteins restrict RNA-directed DNA methylation and antagonize linker histone H1 at euchromatic transposable elements

In plant genomes, transposable elements (TEs) are silenced by CG and non-CG DNA methylation, with non-CG methylation maintained by CMT chromomethylases and the RNA-directed DNA methylation (RdDM) pathway. In Arabidopsis, linker histone H1 differentially influences these pathways, as loss of H1 causes non-CG hypermethylation at pericentromeric TEs but hypomethylation at euchromatic TEs in gene-rich regions. The molecular basis of this antagonism has remained unclear. Here, we show that GH1-HMGAs, a family of H1-related High Mobility Group proteins, bind AT-rich sequences at euchromatic TEs and prevent RdDM-dependent non-CG methylation by limiting siRNA accumulation. Furthermore, GH1-HMGA and H1 compete for chromatin association at these TEs, as loss of GH1-HMGA triggers ectopic H1 redistribution, while loss of H1 increases GH1-HMGA enrichment, providing a mechanistic explanation for the non-CG hypomethylation observed in h1 mutants. Collectively, these findings reveal how GH1-HMGA proteins specifically restrain RdDM activity at euchromatic TEs and elucidate how the H1/GH1-HMGA balance spatially partitions distinct DNA methylation pathways across the genome.

genetics↗

bioRxiv2026

The elongation of Mest transcript into MestXL sustains, but does not initiate, the maternal allele bias of its convergent gene Copg2 during neurogenesis

Precise gene dosage control is critical for establishing cellular identity and development, especially for imprinted genes, where dosage imbalances are linked to severe pathologies such as neurodevelopmental disorders. The Mest/Copg2 imprinted locus is a paradigm for this fine-tuned regulation. While Mest is constitutively expressed from the paternal allele, Copg2 expression shifts from biallelic to a maternal allele bias specifically during neural differentiation, a transition proposed to involve transcriptional interference mediated by the long Mest isoform, MestXL, which extends into the Copg2 locus. However, the mechanisms underlying this allelic switch, and whether factors beyond MestXL contribute, are elusive. To address this, we employed a stem cell-based brain organoid model, integrating multi-omic analyses, 3D chromatin structure mapping, and functional approaches to dissect the regulatory events governing the induction and maintenance of Copg2 maternal allele bias throughout neural lineage specification. Our findings challenge the prevailing model by demonstrating that the maternal allele bias of Copg2 during neural differentiation is not solely driven by MestXL-mediated transcriptional interference. Instead, our data support a temporal and neural stage-specific two-step mechanism: putative enhancer-driven activation of the maternal allele in neural progenitor cells is followed by MestXL-dependent repression of the paternal allele in neuron-enriched stages. This uncovers an unexpected layer of complexity in the regulation of imprinted gene dosage during brain development, with profound implications for understanding the molecular underpinnings of neurodevelopmental disorders.

molecular biology↗

bioRxiv2023

Distinct clades of TELOMERE REPEAT BINDING transcriptional regulators interplay to regulate plant development

TELOMERE REPEAT BINDING proteins (TRBs) are plant-specific transcriptional regulators that combine two DNA-binding domains, the GH1 domain shared with H1 histones that binds to linker DNA and the Myb/SANT domain that specifically recognizes the telobox DNA binding site motif. TRB1, TRB2 and TRB3 proteins recruit the Polycomb group complex 2 (PRC2) to deposit H3K27me3 and JMJ14 to remove H3K4me3 at target genes containing telobox motifs in their promoters to repress transcription. Here, we characterize the function of TRB4 and TRB5, which belong to a separate TRB clade conserved in spermatophytes. TRB4 and TRB5 affect the transcriptional control of several hundred genes involved in developmental responses to environmental cues, the majority of which differ from differentially regulated genes in trb1 trb2 trb3, suggesting distinct modes of action at the chromatin level. Indeed, TRB4 binds to several thousand sites in the genome, mainly at TSS and promoter regions of transcriptionally active and H3K4me3-marked genes but is not enriched at H3K27me3-marked gene bodies. TRB4 physically interacts with the PRC2 component CURLY LEAF (CLF), but, unexpectedly, loss of TRB4 and TRB5 partially suppresses the developmental defects of clf mutant plants, by acting as transcriptional activators of the key flowering genes SOC1 and FT. We further show that TRB4 and TRB1 share multiple target genes and reveal physical and genetic interactions between TRBs of the two distinct clades, collectively unveiling that TRB proteins engage in both positive and negative interactions with other members of the family to regulate plant development through PRC2-dependent and independent mechanisms.

plant biology↗