Cotton’s cold stress memory may hinge on two opposing histone marks

Cotton is a tropical crop by ancestry and a temperate crop by geography, and that mismatch shows up every spring when cold soil meets germinating seed. A review published in Epigenetics & Chromatin argues that the answer to why some cotton plants recover better from chilling than others may lie not in their genes but in chemical tags placed on the histone proteins around which DNA is wound. The authors, led by Mayamiko Masangano and Xiongfeng Ma, propose that two opposing histone marks, the activating H3K4me3 and the repressive H3K27me3, work together to keep cold-responsive genes in a poised state that allows rapid reactivation when temperatures drop again.

The review synthesizes evidence from cotton physiology, transcriptomics, and emerging epigenomic studies, but it is careful about what has been demonstrated and what remains inference. Cotton-specific, time-resolved chromatin datasets that span chilling, recovery, and recurrent chilling are still limited, so several mechanistic conclusions necessarily rest on indirect evidence from cotton studies under other conditions and on well-characterized model plants such as Arabidopsis. The authors frame their central model as a hypothesis that requires direct validation using stress-recovery-re-stress chromatin profiling in cotton itself.

The physiological stakes are clear. Cold stress during seed emergence and early seedling establishment impairs photosynthetic efficiency, damages cellular structures, and reduces yield. Cold destabilizes membrane fluidity, disrupts protein complexes, severely inhibits photosynthetic activity, perturbs plant water status and enzyme activity, and promotes membrane damage and photoinhibition. Even cold-tolerant cultivars such as Zhongmian 36 show marked reductions in transpiration rate, stomatal conductance, net photosynthetic rate, and photosystem II efficiency under cold stress, along with increased Fo/Fm ratios consistent with structural injury to the photosynthetic apparatus.

At the molecular level, low temperature activates a coordinated regulatory network involving calcium signaling, reactive oxygen species accumulation, and mitogen-activated protein kinase cascades. The central module is the ICE-CBF-COR pathway, in which C-repeat binding factor transcription factors bind dehydration-responsive elements in the promoters of cold-responsive genes and induce protective outputs such as late embryogenesis abundant proteins. Additional transcription factor families, including AP2/ERF, NAC, bHLH, MYB, and WRKY, shape downstream cold signaling, and transcriptomic analyses have implicated regulators such as GhPLATZ, GhUVR8, GhNFYA1, and GhNHL69 in cotton cold tolerance.

But transient gene expression changes alone, the review argues, are insufficient to explain sustained stress performance. Plants can store information from past stress exposure and respond more effectively to subsequent events through epigenetic rather than genetic change. The authors define epigenetic priming as a within-generation, somatic state of enhanced responsiveness established after a prior, often mild, cold episode and manifested upon re-exposure within the same plant life cycle. They distinguish this from immediate transcriptional readiness, which operates on a scale of minutes to hours, and from inter- or transgenerational epigenetic inheritance, which remains insufficiently resolved for cold responses in cotton.

H3K27me3, often deposited by Polycomb repressive complex 2, is associated with stable repression, whereas H3K4me3 is linked to transcriptional activation. In cotton, genome-wide profiling shows that H3K4me3 marks are highly concentrated downstream of transcription start sites and often extend into gene bodies, a pattern typical of genes that are currently being transcribed. H3K27me3 typically covers larger gene-body areas and is strongly associated with Polycomb-mediated transcriptional repression. Comparative analyses of the A and D subgenomes of allotetraploid cotton reveal that although the distribution of H3K27me3 is predominantly conserved, H3K4me3 exhibits significant subgenome-specific variation, with diminished promoter-proximal enrichment and heightened distal intergenic marking in the A subgenome, indicating epigenomic asymmetry after allopolyploidisation.

The functional consequences of these patterns are evident in transcriptional divergence. Studies of homeologous gene pairs demonstrate that highly expressed homeologs are consistently enriched for H3K4me3, while their lowly expressed counterparts preferentially accumulate H3K27me3, reinforcing subfunctionalisation and promoting long-term genome stability in polyploid cotton. However, the review stresses that most genome-wide profiling studies demonstrate associations between histone-mark distribution and transcriptional status rather than direct causality. Causal inference requires functional perturbation of histone writers, erasers, or readers combined with time-resolved transcriptomic and chromatin profiling.

The evidence for H3K4me3 dynamics under cold stress in cotton is emerging but incomplete. A recent study profiled genome-wide H3K4me3 and H3K9ac in upland cotton seedlings under acute cold stress using CUT&Tag and reported that changes in these marks correlate with cold stress-responsive gene activation. Cotton dehydration-stress memory studies report that subsets of stress-inducible genes retain elevated H3K4me3 after recovery, enabling accelerated reactivation during subsequent stress events. This provides a precedent that H3K4me3 retention can participate in within-generation priming in cotton, but whether recurrent chilling elicits analogous dynamics remains untested. In Arabidopsis, cold exposure triggers rapid, gene-specific redistribution of H3K4me3 that accompanies the activation of cold-responsive genes during acclimation, supporting the plausibility of a similar regulatory role during chilling in cotton.

On the repressive side, H3K27me3 keeps cold-responsive genes inactive under favorable growth conditions, preventing inappropriate expression of cold-effector genes that would divert energy from growth. Upon cold exposure, chromatin state can change rapidly and in a locus-specific manner, including selective decreases in H3K27me3 at key cold-responsive loci. In Arabidopsis, H3K27me3 levels decline within hours at promoters of genes such as COR15A, KIN1, and GOLS3, which encode functions linked to membrane stabilization, osmoprotection, and cryotolerance. Importantly, H3K27me3 loss does not necessarily coincide with H3K4me3 gain, arguing against a simple one-to-one antagonistic exchange. Some Jumonji C family demethylases contribute to H3K27me3 removal during cold responses, and in Arabidopsis impaired ELF6 function compromises reactivation of some COR genes during repeated cold exposure. For cotton, however, this remains an extrapolative model rather than a demonstrated mechanism.

The review’s most provocative concept is bivalent chromatin, genomic regions that show enrichment of both the activation-associated mark H3K4me3 and the repression-associated mark H3K27me3. This configuration, first described at key developmental genes in mammalian embryonic stem cells and also reported as bivalency-like chromatin in plant systems, may keep genes in a poised state, allowing rapid activation under environmental cues while maintaining repression under normal growth conditions. The authors propose that selected cold-responsive regulatory genes in cotton may retain activation-associated H3K4me3 while undergoing partial or delayed resetting of H3K27me3 during recovery, supporting faster transcriptional re-induction during recurrent chilling without causing permanent activation of stress pathways. But they caution that co-enrichment detected from bulk ChIP-seq or CUT&Tag data does not necessarily prove that both marks occupy the same nucleosome, allele, or cell type, and that apparent co-marking may reflect population-level averaging, asymmetric nucleosome marking, or tissue and cell-type heterogeneity. Cotton-specific cold datasets capable of distinguishing true co-occupancy from these alternatives remain limited, and the authors call for sequential ChIP or CUT&Tag, multi-mark profiling, cell- or tissue-specific chromatin assays, and homeolog-aware mapping across cold exposure, recovery, and re-stress to test the model directly.

Subject of Research: Epigenetic regulation of cold stress responses in cotton

Article Title: Bivalent chromatin states and epigenetic priming in cotton: the role of H3K4me3 and H3K27me3 in cold stress memory and resilience

Article References: Masangano, M., Nasre, A., Lakew, F. D., Gelaye, Y., Gao, Y., Zhang, Y., Cheng, G., Arshad, U., Ziwei, L., Yang, L., Kang, M., Liang, Y., Cao, X., Song, X., Miao, C., Liubei, B., Shihong, Y., Pei, X., Ren, X., … Ma, X. (2026). Bivalent chromatin states and epigenetic priming in cotton: the role of H3K4me3 and H3K27me3 in cold stress memory and resilience. Epigenetics & Chromatin, 19(1), Article 30. https://doi.org/10.1186/s13072-026-00680-3

Image Credits: AI Generated

DOI: 10.1186/s13072-026-00680-3

Keywords: cotton, H3K4me3, H3K27me3, bivalent chromatin, epigenetic priming, cold stress, Polycomb, histone modification, allotetraploid, chromatin memory, Gossypium hirsutum, stress resilience