Biology subjects

Feierman, E. R.

Publications and source records attributed to Feierman, E. R..

3 recordsLinked to original sources

bioRxiv2026

Mechanisms controlling the deposition and dynamics of histone variant H2BE

Histone variants shape chromatin structure and gene regulation and their deposition and localization in chromatin are tightly controlled. H2BE is the only known widely expressed mammalian H2B variant and localizes to transcription start sites to control chromatin accessibility and cognitive function. However, the mechanisms governing H2B variant incorporation into chromatin remain unclear. Here, we define the regulatory framework controlling H2BE incorporation, localization, and eviction in neuronal chromatin. We identify the BAF remodeling complex and the transcription factor SP1 as key drivers of H2BE deposition at specific genomic loci. We further show that FACT maintains H2BE enrichment at transcription start sites by preventing its distribution into gene bodies, while the histone chaperone NAP1L4 mediates H2BE eviction from chromatin. Comparative analysis with H2A.Z reveals that BAF, SP1 and NAP1L4 exert H2BE-specific functions, while FACT functions more broadly across histone variants. Finally, we define the H2BE-dependent transcriptional effects of it chaperones. Together, these findings uncover the first chaperones governing H2B variant incorporation and define a highly complex mechanism responsible for H2BE regulation in chromatin. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/719605v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@199fd10org.highwire.dtl.DTLVardef@b561c1org.highwire.dtl.DTLVardef@24ef4corg.highwire.dtl.DTLVardef@da8152_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThe BAF complex controls H2BE incorporation. C_LIO_LISP1 promotes locus-specific incorporation of H2BE. C_LIO_LIFACT prevents H2BE accumulation in genic regions. C_LIO_LINAP1L4 mediates eviction of H2BE from chromatin. C_LI

genetics↗

bioRxiv2024

Histone variant H2BE controls activity-dependent gene expression and homeostatic scaling

A cells ability to respond and adapt to environmental stimuli relies in part on transcriptional programs controlled by histone proteins. Histones affect transcription through numerous mechanisms including through replacement with variant forms that carry out specific functions. We recently identified the first widely expressed H2B histone variant, H2BE and found that it promotes transcription and is critical for neuronal function and long-term memory. However, how H2BE is regulated by extracellular stimuli and whether it controls activity-dependent transcription and cellular plasticity remain unknown. We used CUT&Tag and RNA-sequencing of primary neurons, single-nucleus sequencing of cortical tissue, and multielectrode array recordings to interrogate the expression of H2BE in response to stimuli and the role of H2BE in activity-dependent gene expression and plasticity. We find that unlike Further, we show that neurons lacking H2BE are unable to mount proper long-term activity-dependent transcriptional responses both in cultured neurons and in animal models. Lastly, we demonstrate that H2BE knockout neurons fail to undergo the electrophysiological changes associated with homeostatic plasticity in neurons after long-term stimulation. In summary, these data demonstrate that H2BE expression is inversely correlated to activity and necessary for long-term activity-dependent responses, revealing the first instance of a histone variant involved in the homeostatic plasticity response in neurons.

genetics↗

bioRxiv2024

Histone variant H2BE enhances chromatin accessibility in neurons to promote synaptic gene expression and long-term memory

Regulation of histone proteins affects gene expression through multiple mechanisms including exchange with histone variants. However, widely expressed variants of H2B remain elusive. Recent findings link histone variants to neurological disorders, yet few are well studied in the brain. We applied new tools including novel antibodies, biochemical assays, and sequencing approaches to reveal broad expression of the H2B variant H2BE, and defined its role in regulating chromatin structure, neuronal transcription, and mouse behavior. We find that H2BE is enriched at promoters and a single unique amino acid allows it to dramatically enhance chromatin accessibility. Lastly, we show that H2BE is critical for synaptic gene expression and long-term memory. Together, these data reveal a novel mechanism linking histone variants to chromatin regulation, neuronal function, and memory. This work further identifies the first widely expressed H2B variant and uncovers a single histone amino acid with profound effects on genomic structure.

genetics↗