A non-canonical role of the inner kinetochore in regulating sister-chromatid cohesion at centromeres.

The 16-subunit Constitutive Centromere-associated Network (CCAN)-based inner kinetochore is well-known for connecting centromeric chromatin to the spindle-binding outer kinetochore. Here, we report a non-canonical role for the inner kinetochore in directly regulating sister-chromatid cohesion at centromeres. We provide biochemical, X-ray crystal structure, and intracellular ectopic localization evidence that the inner kinetochore directly binds cohesin, a ring-shaped multi-subunit complex that holds sister chromatids together from S-phase until anaphase onset. This interaction is mediated by binding of the 5-subunit CENP-OPQUR sub-complex of CCAN to the Scc1-SA2 sub-complex of cohesin. Mutation in the CENP-U subunit of the CENP-OPQUR complex that abolishes its binding to the composite interface between Scc1 and SA2 weakens centromeric cohesion, leading to premature separation of sister chromatids during delayed metaphase. We further show that CENP-U competes with the cohesin release factor Wapl for binding the interface of Scc1-SA2, and that the cohesion-protecting role for CENP-U can be bypassed by depleting Wapl. Taken together, this study reveals an inner kinetochore-bound pool of cohesin, which strengthens centromeric sister-chromatid cohesion to resist metaphase spindle pulling forces.

Molecular mechanism and functional significance of Wapl interaction with the Cohesin complex.

The ring-shaped Cohesin complex, consisting of core subunits Smc1, Smc3, Scc1, and SA2 (or its paralog SA1), topologically entraps two duplicated sister DNA molecules to establish sister chromatid cohesion in S-phase. It remains largely elusive how the Cohesin release factor Wapl binds the Cohesin complex, thereby inducing Cohesin disassociation from mitotic chromosomes to allow proper resolution and separation of sister chromatids. Here, we show that Wapl uses two structural modules containing the FGF motif and the YNARHWN motif, respectively, to simultaneously bind distinct pockets in the extensive composite interface between Scc1 and SA2. Strikingly, only when both docking modules are mutated, Wapl completely loses the ability to bind the Scc1-SA2 interface and release Cohesin, leading to erroneous chromosome segregation in mitosis. Surprisingly, Sororin, which contains a conserved FGF motif and functions as a master antagonist of Wapl in S-phase and G2-phase, does not bind the Scc1-SA2 interface. Moreover, Sgo1, the major protector of Cohesin at mitotic centromeres, can only compete with the FGF motif but not the YNARHWN motif of Wapl for binding Scc1-SA2 interface. Our data uncover the molecular mechanism by which Wapl binds Cohesin to ensure precise chromosome segregation.

The RPA-RNF20-SNF2H cascade promotes proper chromosome segregation and homologous recombination repair.

The human tumor suppressor Ring finger protein 20 (RNF20)-mediated histone H2B monoubiquitination (H2Bub) is essential for proper chromosome segregation and DNA repair. However, what is the precise function and mechanism of RNF20-H2Bub in chromosome segregation and how this pathway is activated to preserve genome stability remain unknown. Here, we show that the single-strand DNA-binding factor Replication protein A (RPA) interacts with RNF20 mainly in the S and G2/M phases and recruits RNF20 to mitotic centromeres in a centromeric R-loop-dependent manner. In parallel, RPA recruits RNF20 to chromosomal breaks upon DNA damage. Disruption of the RPA-RNF20 interaction or depletion of RNF20 increases mitotic lagging chromosomes and chromosome bridges and impairs BRCA1 and RAD51 loading and homologous recombination repair, leading to elevated chromosome breaks, genome instability, and sensitivities to DNA-damaging agents. Mechanistically, the RPA-RNF20 pathway promotes local H2Bub, H3K4 dimethylation, and subsequent SNF2H recruitment, ensuring proper Aurora B kinase activation at centromeres and efficient loading of repair proteins at DNA breaks. Thus, the RPA-RNF20-SNF2H cascade plays a broad role in preserving genome stability by coupling H2Bub to chromosome segregation and DNA repair.

Histone H2A phosphorylation recruits topoisomerase IIα to centromeres to safeguard genomic stability.

Chromosome segregation in mitosis requires the removal of catenation between sister chromatids. Timely decatenation of sister DNAs at mitotic centromeres by topoisomerase IIα (TOP2A) is crucial to maintain genomic stability. The chromatin factors that recruit TOP2A to centromeres during mitosis remain unknown. Here, we show that histone H2A Thr-120 phosphorylation (H2ApT120), a modification generated by the mitotic kinase Bub1, is necessary and sufficient for the centromeric localization of TOP2A. Phosphorylation at residue-120 enhances histone H2A binding to TOP2A in vitro. The C-gate and the extreme C-terminal region are important for H2ApT120-dependent localization of TOP2A at centromeres. Preventing H2ApT120-mediated accumulation of TOP2A at mitotic centromeres interferes with sister chromatid disjunction, as evidenced by increased frequency of anaphase ultra-fine bridges (UFBs) that contain catenated DNA. Tethering TOP2A to centromeres bypasses the requirement for H2ApT120 in suppressing anaphase UFBs. These results demonstrate that H2ApT120 acts as a landmark that recruits TOP2A to mitotic centromeres to decatenate sister DNAs. Our study reveals a fundamental role for histone phosphorylation in resolving centromere DNA entanglements and safeguarding genomic stability during mitosis.

Dynamic Evolution of Antisite Defect and Coupling Anionic Redox in High-Voltage Ultrahigh-Ni Cathode.

High-voltage ultrahigh-Ni cathodes (LiNixCoyMn1-x-yO2, x≥0.9) can significantly enhance the energy density and cost-effectiveness of Li-ion batteries beyond current levels. However, severe Li-Ni antisite defects and their undetermined dynamic evolutions during high-voltage cycling limit the further development of these ultrahigh-Ni cathodes. In this study, we quantify the dynamic evolutions of the Li-Ni antisite defect using operando neutron diffraction and reveal its coupling relationship with anionic redox, another critical challenge restricting ultrahigh-Ni cathodes. We detect a clear Ni migration coupled with an unstable oxygen lattice, which accompanies the oxidation of oxygen anions at high voltages. Based on these findings, we propose that minimized Li-Ni antisite defects and controlled Ni migrations are essential for achieving stable high-voltage cycling structures in ultrahigh-Ni cathodes. This is further demonstrated by the optimized ultrahigh-Ni cathode, where reduced dynamic evolutions of the Li-Ni antisite defect effectively inhibit the anionic redox, enhancing the 4.5 V cycling stability.

Localizing Oxygen Lattice Evolutions Eliminates Oxygen Release and Voltage Decay in All-Mn-Based Li-Rich Cathodes.

All-Mn-based Li-rich cathodes Li2 MnO3 have attracted extensive attention because of their cost advantage and ultrahigh theoretical capacity. However, the unstable anionic redox reaction (ARR), which involves irreversible oxygen releases, causes declines in cycling capacity and intercalation potential, thus hindering their practical applications. Here, it is proposed that introducing stacking-fault defects into the Li2 MnO3 can localize oxygen lattice evolutions and stabilize the ARR, eliminating oxygen releases. The thus-made cathode has a highly reversible capacity (320 mA h g-1 ) and achieves excellent cycling stability. After 100 cycles, the capacity retention rate is 86% and the voltage decay is practically eliminated at 0.19 mV per cycle. Attributing to the stable ARR, samples show reduced stress-strain and phase transitions. Neutron pair distribution function (nPDF) measurements indicate that there is a structure response of localized oxygen lattice distortion to the ARR and the average oxygen lattice framework is well-preserved which is a prerequisite for the high cycle reversibility.

Identification of cuproptosis-related asthma diagnostic genes by WGCNA analysis and machine learning.

OBJECTIVE: Cuproptosis is the latest novel form of cell death. However, the relationship between asthma and cuproptosis is not fully understood. METHODS: In this study, we screened differentially expressed cuproptosis-related genes from the Gene Expression Omnibus (GEO) database and performed immune infiltration analysis. Subsequently, patients with asthma were typed and analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG). Weighted gene co-expression network analysis (WGCNA) was performed to calculate the module-trait correlations, and the hub genes of the intersection were taken to construct machine learning (XGB, SVM, RF, GLM). Finally, we used TGF-ß to establish a BEAS-2B asthma model to observe the expression levels of hub genes. RESULTS: Six cuproptosis-related genes were obtained. Immune-infiltration analysis shows that cuproptosis-related genes are associated with a variety of biological functions. We classified asthma patients into two subtypes based on the expression of cuproptosis-related genes and found significant Gene Ontology (GO) and immune function differences between the different subtypes. WGCNA selected 2 significant modules associated with disease features and typing. Finally, we identified TRIM25, DYSF, NCF4, ABTB1, CXCR1 as asthma biomarkers by taking the intersection of the hub genes of the 2 modules and constructing a 5-genes signature, which nomograph, decision curve analysis (DCA) and calibration curves, receiver operating characteristic curve (ROC) showed high efficiency in diagnosing the probability of survival of asthma patients. Finally, in vitro experiments have shown that DYSF and CXCR1 expression is up expressed in asthma. CONCLUSIONS: Our study provides further directions for studying the molecular mechanism of asthma.

CMOS-Compatible Electronic-Plasmonic Transducers Based on Plasmonic Tunnel Junctions and Schottky Diodes.

To develop methods to generate, manipulate, and detect plasmonic signals by electrical means with complementary metal-oxide-semiconductor (CMOS)-compatible materials is essential to realize on-chip electronic-plasmonic transduction. Here, electrically driven, CMOS-compatible electronic-plasmonic transducers with Al-AlOX -Cu tunnel junctions as the excitation source of surface plasmon polaritons (SPPs) and Si-Cu Schottky diodes as the detector of SPPs, connected via plasmonic strip waveguides of Cu, are demonstrated. Remarkably, the electronic-plasmonic transducers exhibit overall transduction efficiency of 1.85 ± 0.03%, five times higher than previously reported transducers with two tunnel junctions (metal-insulator-metal (MIM)-MIM transducers) where SPPs are detected based on optical rectification. The result establishes a new platform to convert electronic signals to plasmonic signals via electrical means, paving the way toward CMOS-compatible plasmonic components.

Cuproptosis-related lncRNA predict prognosis and immune response of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) accounts for 50% of lung cancers, with high mortality and poor prognosis. Long non-coding RNA (lncRNA) plays a vital role in the progression of tumors. Cuproptosis is a newly discovered form of cell death that is highly investigated. Therefore, in the present study, we aimed to investigate the role of cuproptosis-related lncRNA signature in clinical prognosis prediction and immunotherapy and the relationship with drug sensitivity. MATERIAL AND METHODS: Genomic and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and cuproptosis-related genes were obtained from cuproptosis-related studies. The prognostic signature was constructed by co-expression analysis and Cox regression analysis. Patients were divided into high and low risk groups, and then, a further series of model validations were carried out to assess the prognostic value of the signature. Subsequently, lncRNAs were analyzed for gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes Enrichment (KEGG), immune-related functions, and tumor mutation burden (TMB). Finally, we used tumor immune dysfunction and exclusion (TIDE) algorithms on immune escape and immunotherapy of cuproptosis-related lncRNAs, thereby identifying its sensitivity toward potential drugs for LUAD. RESULTS: A total of 16 cuproptosis-related lncRNAs were obtained, and a prognostic signature was developed. We found that high-risk patients had worse overall survival (OS) and progression-free survival (PFS) and higher mortality. Independent prognostic analyses, ROC, C-index, and nomogram showed that the cuproptosis-related lncRNAs can accurately predict the prognosis of patients. The nomogram and heatmap showed a distinct distribution of the high- and low-risk cuproptosis-related lncRNAs. Enrichment analysis showed that the biological functions of lncRNAs are associated with tumor development. We also found that immune-related functions, such as antiviral activity, were suppressed in high-risk patients who had mutations in oncogenes. OS was poorer in patients with high TMB. TIDE algorithms showed that high-risk patients have a greater potential for immune escape and less effective immunotherapy. CONCLUSION: To conclude, the 16 cuproptosis-related lncRNAs can accurately predict the prognosis of patients with LUAD and may provide new insights into clinical applications and immunotherapy.

Aurora B kinase activity-dependent and -independent functions of the chromosomal passenger complex in regulating sister chromatid cohesion.

The chromosomal passenger complex (CPC) is a master regulator of mitosis. CPC consists of inner centromere protein (INCENP), Survivin, Borealin, and the kinase Aurora B and plays key roles in regulating kinetochore-microtubule attachments and spindle assembly checkpoint signaling. However, the role of CPC in sister chromatid cohesion, mediated by the cohesin complex, remains incompletely understood. Here, we show that Aurora B kinase activity contributes to centromeric cohesion protection partly through promoting kinetochore localization of the kinase Bub1. Interestingly, disrupting the interaction of INCENP with heterochromatin protein 1 (HP1) in HeLa cells selectively weakens cohesion at mitotic centromeres without detectably reducing the kinase activity of Aurora B. Thus, through this INCENP-HP1 interaction, the CPC also protects centromeric cohesion independently of Aurora B kinase activity. Moreover, the requirement for the INCENP-HP1 interaction in centromeric cohesion protection can be bypassed by tethering HP1 to centromeres or by depleting the cohesin release factor Wapl. We provide further evidence suggesting that the INCENP-HP1 interaction protects centromeric cohesion by promoting the centromere localization of Haspin, a protein kinase that antagonizes Wapl activity at centromeres. Taken together, this study identifies Aurora B kinase activity-dependent and -independent roles for the CPC in regulating centromeric cohesion during mitosis in human cells.

A positive feedback mechanism ensures proper assembly of the functional inner centromere during mitosis in human cells.

The inner centromere region of a mitotic chromosome critically regulates sister chromatid cohesion and kinetochore-microtubule attachments. However, the molecular mechanism underlying inner centromere assembly remains elusive. Here, using CRISPR/Cas9-based gene editing in HeLa cells, we disrupted the interaction of Shugoshin 1 (Sgo1) with histone H2A phosphorylated on Thr-120 (H2ApT120) to selectively release Sgo1 from mitotic centromeres. Interestingly, cells expressing the H2ApT120-binding defective mutant of Sgo1 have an elevated rate of chromosome missegregation accompanied by weakened centromeric cohesion and decreased centromere accumulation of the chromosomal passenger complex (CPC), an integral part of the inner centromere and a key player in the correction of erroneous kinetochore-microtubule attachments. When artificially tethered to centromeres, a Sgo1 mutant defective in binding protein phosphatase 2A (PP2A) is not able to support proper centromeric cohesion and CPC accumulation, indicating that the Sgo1-PP2A interaction is essential for the integrity of mitotic centromeres. We further provide evidence indicating that Sgo1 protects centromeric cohesin to create a binding site for the histone H3-associated protein kinase Haspin, which not only inhibits the cohesin release factor Wapl and thereby strengthens centromeric cohesion but also phosphorylates histone H3 at Thr-3 to position CPC at inner centromeres. Taken together, our findings reveal a positive feedback-based mechanism that ensures proper assembly of the functional inner centromere during mitosis. They further suggest a causal link between centromeric cohesion defects and chromosomal instability in cancer cells.

HP1 links centromeric heterochromatin to centromere cohesion in mammals.

Heterochromatin protein-1 (HP1) is a key component of heterochromatin. Reminiscent of the cohesin complex which mediates sister-chromatid cohesion, most HP1 proteins in mammalian cells are displaced from chromosome arms during mitotic entry, whereas a pool remains at the heterochromatic centromere region. The function of HP1 at mitotic centromeres remains largely elusive. Here, we show that double knockout (DKO) of HP1α and HP1γ causes defective mitosis progression and weakened centromeric cohesion. While mutating the chromoshadow domain (CSD) prevents HP1α from protecting sister-chromatid cohesion, centromeric targeting of HP1α CSD alone is sufficient to rescue the cohesion defects in HP1 DKO cells. Interestingly, HP1-dependent cohesion protection requires Haspin, an antagonist of the cohesin-releasing factor Wapl. Moreover, HP1α CSD directly binds the N-terminal region of Haspin and facilitates its centromeric localization. The need for HP1 in cohesion protection can be bypassed by centromeric targeting of Haspin or inhibiting Wapl activity. Taken together, these results reveal a redundant role for HP1α and HP1γ in the protection of centromeric cohesion through promoting Haspin localization at mitotic centromeres in mammalian cells.

A kinase-dependent role for Haspin in antagonizing Wapl and protecting mitotic centromere cohesion.

Sister-chromatid cohesion mediated by the cohesin complex is fundamental for precise chromosome segregation in mitosis. Through binding the cohesin subunit Pds5, Wapl releases the bulk of cohesin from chromosome arms in prophase, whereas centromeric cohesin is protected from Wapl until anaphase onset. Strong centromere cohesion requires centromeric localization of the mitotic histone kinase Haspin, which is dependent on the interaction of its non-catalytic N-terminus with Pds5B. It remains unclear how Haspin fully blocks the Wapl-Pds5B interaction at centromeres. Here, we show that the C-terminal kinase domain of Haspin (Haspin-KD) binds and phosphorylates the YSR motif of Wapl (Wapl-YSR), thereby directly inhibiting the YSR motif-dependent interaction of Wapl with Pds5B. Cells expressing a Wapl-binding-deficient mutant of Haspin or treated with Haspin inhibitors show centromeric cohesion defects. Phospho-mimetic mutation in Wapl-YSR prevents Wapl from binding Pds5B and releasing cohesin. Forced targeting Haspin-KD to centromeres partly bypasses the need for Haspin-Pds5B interaction in cohesion protection. Taken together, these results indicate a kinase-dependent role for Haspin in antagonizing Wapl and protecting centromeric cohesion in mitosis.

NudCL2 is an Hsp90 cochaperone to regulate sister chromatid cohesion by stabilizing cohesin subunits.

Sister chromatid cohesion plays a key role in ensuring precise chromosome segregation during mitosis, which is mediated by the multisubunit cohesin complex. However, the molecular regulation of cohesin subunits stability remains unclear. Here, we show that NudCL2 (NudC-like protein 2) is essential for the stability of cohesin subunits by regulating Hsp90 ATPase activity in mammalian cells. Depletion of NudCL2 induces mitotic defects and premature sister chromatid separation and destabilizes cohesin subunits that interact with NudCL2. Similar defects are also observed upon inhibition of Hsp90 ATPase activity. Interestingly, ectopic expression of Hsp90 efficiently rescues the protein instability and functional deficiency of cohesin induced by NudCL2 depletion, but not vice versa. Moreover, NudCL2 not only binds to Hsp90, but also significantly modulates Hsp90 ATPase activity and promotes the chaperone function of Hsp90. Taken together, these data suggest that NudCL2 is a previously undescribed Hsp90 cochaperone to modulate sister chromatid cohesion by stabilizing cohesin subunits, providing a hitherto unrecognized mechanism that is crucial for faithful chromosome segregation during mitosis.

Tetragonal and trigonal Mo2B2 monolayers: two new low-dimensional materials for Li-ion and Na-ion batteries.

In this study, we report two new Mo2B2 monolayers and investigate their stabilities, electronic structures, lattice dynamics, and properties as anode materials for energy storage by using the crystal structure prediction technique and first-principles method. The calculated phonon spectra and electrical structures indicate that our predicted tetragonal and trigonal Mo2B2 (tetr- and tri-Mo2B2) monolayers possess excellent electronic conductivity and great stability. The adsorption energies of Li/Na on them are negative enough to ensure stability and safety under operating conditions. Besides, tetr-Mo2B2 possesses a theoretical specific capacity of ∼251 mA h g-1 for both Li- and Na-ion batteries (LIBs and NIBs), while tri-Mo2B2 possesses ∼251 and ∼188 mA h g-1 for LIBs and NIBs, respectively. The diffusion energy barriers of Li/Na over tetr- (0.029/0.010 eV) and tri- (0.023/0.013 eV) Mo2B2 are very small, indicating their excellent charge/discharge capability. In addition, the low electrode potential of Li/Na-intercalated tetr- and tri-Mo2B2 is beneficial to their performance as anode materials. This work is of great importance for widening the families of both anode materials for LIBs/NIBs and two-dimensional transition metal borides.

Stabilizing the Oxygen Lattice and Reversible Oxygen Redox Chemistry through Structural Dimensionality in Lithium-Rich Cathode Oxides.

Lattice-oxygen redox (l-OR) has become an essential companion to the traditional transition-metal (TM) redox charge compensation to achieve high capacity in Li-rich cathode oxides. However, the understanding of l-OR chemistry remains elusive, and a critical question is the structural effect on the stability of l-OR reactions. Herein, the coupling between l-OR and structure dimensionality is studied. We reveal that the evolution of the oxygen-lattice structure upon l-OR in Li-rich TM oxides which have a three-dimensional (3D)-disordered cation framework is relatively stable, which is in direct contrast to the clearly distorted oxygen-lattice framework in Li-rich oxides which have a two-dimensional (2D)/3D-ordered cation structure. Our results highlight the role of structure dimensionality in stabilizing the oxygen lattice in reversible l-OR, which broadens the horizon for designing high-energy-density Li-rich cathode oxides with stable l-OR chemistry.

Superconductivity in two-dimensional phosphorus carbide (ß0-PC).

Two-dimensional (2D) boron has been predicted to show superconductivity. However, intrinsic 2D carbon and phosphorus have not been reported to be superconductors, which has inspired us to study the superconductivity of their mixture. Here we performed first-principles calculations for the electronic structure, phonon dispersion, and electron-phonon coupling of the metallic phosphorus carbide monolayer, ß0-PC. The results show that it is an intrinsic phonon-mediated superconductor, with an estimated superconducting temperature Tc of ∼13 K. The main contribution to the electron-phonon coupling is from the out-of-plane vibrations of phosphorus. A Kohn anomaly on the first acoustic branch is observed. The superconducting related physical quantities are found to be tunable by applying strain or by carrier doping.

Hexagonal Ti2B2 monolayer: a promising anode material offering high rate capability for Li-ion and Na-ion batteries.

Combining the first-principles density functional method and crystal structure prediction techniques, we report a series of hexagonal two-dimensional transition metal borides including Sc2B2, Ti2B2, V2B2, Cr2B2, Y2B2, Zr2B2, and Mo2B2. Their dynamic and thermal stabilities are testified by phonon and molecular dynamics simulations. We investigate the potential of the two-dimensional Ti2B2 monolayer as an anode material for Li-ion and Na-ion batteries. The Ti2B2 monolayer possesses high theoretical specific capacities of 456 and 342 mA h g-1 for Li and Na, respectively. The very high Li/Na diffusivity with an ultralow energy barrier of 0.017/0.008 eV indicates an excellent charge-discharge capability. In addition, good electronic conductivity during the whole lithiation process is found by electronic structure calculations. The very small change in volume after the adsorption of one, two, and three layers of Li and Na ions indicates that the Ti2B2 monolayer is robust. These results highlight the suitability of Ti2B2 monolayer as well as the other two-dimensional transition metal borides as excellent anode materials for both Li-ion and Na-ion batteries.

Polo-like kinase-1 triggers histone phosphorylation by Haspin in mitosis.

Histone modifications coordinate the chromatin localization of key regulatory factors in mitosis. For example, mitotic phosphorylation of Histone H3 threonine-3 (H3T3ph) by Haspin creates a binding site for the chromosomal passenger complex (CPC). However, how these histone modifications are spatiotemporally controlled during the cell cycle is unclear. Here we show that Plk1 binds to Haspin in a Cdk1-phosphorylation-dependent manner. Reducing Plk1 activity decreases the phosphorylation of Haspin and inhibits H3T3ph, particularly in prophase, suggesting that Plk1 is required for initial activation of Haspin in early mitosis. These studies demonstrate that Plk1 can positively regulate CPC recruitment in mitosis.

A phospho/methyl switch at histone H3 regulates TFIID association with mitotic chromosomes.

Histone methylation patterns are correlated with eukaryotic gene transcription. High-affinity binding of the plant homeodomain (PHD) of TFIID subunit TAF3 to trimethylated lysine-4 of histone H3 (H3K4me3) is involved in promoter recruitment of this basal transcription factor. Here, we show that for transcription activation the PHD of TAF3 can be replaced by PHDs of other high-affinity H3K4me3 binders. Interestingly, H3K4me3 binding of TFIID and the TAF3-PHD is decreased by phosphorylation of the adjacent threonine residue (H3T3), which coincides with mitotic inhibition of transcription. Ectopic expression of the H3T3 kinase haspin repressed TAF3-mediated transcription of endogenous and of reporter genes and decreased TFIID association with chromatin. Conversely, immunofluorescence and live-cell microscopy studies showed an increased association of TFIID with mitotic chromosomes upon haspin knockdown. Based on our observations, we propose that a histone H3 phospho-methyl switch regulates TFIID-mediated transcription during mitotic progression of the cell cycle.