# Recycling of modified H2A-H2B provides short-term memory of chromatin states **Authors:** Valentin Flury, Nazaret Reverón-Gómez, Nicolas Alcaraz, Kathleen R. Stewart-Morgan, Alice Wenger, Robert J. Klose, Anja Groth PMC · DOI: 10.1016/j.cell.2023.01.007 · Cell · 2023-03-02 ## TL;DR The study shows how histone H2A-H2B modifications are recycled during DNA replication, helping to preserve chromatin states and cell identity. ## Contribution The work reveals the independent recycling of H2A-H2B modifications during replication and their role in restoring chromatin states. ## Key findings - H2A-H2B modifications are recycled during DNA replication independently of H3-H4. - H2AK119ub1 helps restore H3K27me3 after replication. - H2A.Z and H2BK120ub1 mark nascent chromatin before transcription resumes. ## Abstract Chromatin landscapes are disrupted during DNA replication and must be restored faithfully to maintain genome regulation and cell identity. The histone H3-H4 modification landscape is restored by parental histone recycling and modification of new histones. How DNA replication impacts on histone H2A-H2B is currently unknown. Here, we measure H2A-H2B modifications and H2A.Z during DNA replication and across the cell cycle using quantitative genomics. We show that H2AK119ub1, H2BK120ub1, and H2A.Z are recycled accurately during DNA replication. Modified H2A-H2B are segregated symmetrically to daughter strands via POLA1 on the lagging strand, but independent of H3-H4 recycling. Post-replication, H2A-H2B modification and variant landscapes are quickly restored, and H2AK119ub1 guides accurate restoration of H3K27me3. This work reveals epigenetic transmission of parental H2A-H2B during DNA replication and identifies cross talk between H3-H4 and H2A-H2B modifications in epigenome propagation. We propose that rapid short-term memory of recycled H2A-H2B modifications facilitates restoration of stable H3-H4 chromatin states. •Histone H2A-H2B are recycled during DNA replication independent of H3-H4•H2A.Z and H2BK120ub1 mark nascent chromatin prior to transcription re-start•H2A-H2B modification and variant landscapes are restored rapidly after replication•H2AK119ub1 facilitates accurate and timely restoration of H3K27me3 post-replication Histone H2A-H2B are recycled during DNA replication independent of H3-H4 H2A.Z and H2BK120ub1 mark nascent chromatin prior to transcription re-start H2A-H2B modification and variant landscapes are restored rapidly after replication H2AK119ub1 facilitates accurate and timely restoration of H3K27me3 post-replication Accurate recycling of histones during DNA replication is crucial for restoring chromatin landscape and cell identity. A new study provides mechanistic insights into the elusive replication-dependent recycling of H2A-H2B and the associated histone modifications. ## Linked entities - **Proteins:** H2AC18 (H2A clustered histone 18), H2BC21 (H2B clustered histone 21), H2AZ1 (H2A.Z variant histone 1), POLA1 (DNA polymerase alpha 1, catalytic subunit), RLN3 (relaxin 3), CCDC6 (coiled-coil domain containing 6) ## Full-text entities - **Genes:** Lif (leukemia inhibitory factor) [NCBI Gene 16878], Bap1 (Brca1 associated protein 1) [NCBI Gene 104416] {aka 2300006C11Rik, mKIAA0272, uch-x4}, Rnf2 (ring finger protein 2) [NCBI Gene 19821] {aka Ring1B, dinG}, LIF (LIF interleukin 6 family cytokine) [NCBI Gene 3976] {aka CDF, DIA, HILDA, MLPLI}, Pola1 (polymerase (DNA directed), alpha 1) [NCBI Gene 18968] {aka Pola}, Ring1 (ring finger protein 1) [NCBI Gene 19763] {aka Ring1A}, RNF40 (ring finger protein 40) [NCBI Gene 9810] {aka BRE1B, RBP95, STARING}, Pcgf6 (polycomb group ring finger 6) [NCBI Gene 71041] {aka 4933407A11Rik, MBLR, Rnf134}, Pcgf1 (polycomb group ring finger 1) [NCBI Gene 69837] {aka 2010002K04Rik, Nspc1}, Mcm2 (Minichromosome maintenance 2) [NCBI Gene 40973] {aka CG7538, DmMCM2, DmMcm2, DmeMCM2, Dmel\CG7538, MCM2-7}, spk (spike) [NCBI Gene 5657015], Pcgf2 (polycomb group ring finger 2) [NCBI Gene 22658] {aka Mel18, Rnf110, Zfp144, mel-18}, Pcna (proliferating cell nuclear antigen) [NCBI Gene 18538], Rnase1 (ribonuclease, RNase A family, 1 (pancreatic)) [NCBI Gene 19752] {aka Rib-1, Rib1}, POLA1 (DNA polymerase alpha 1, catalytic subunit) [NCBI Gene 5422] {aka NSX, PDR, POLA, VEODS, p180}, Rybp (RING1 and YY1 binding protein) [NCBI Gene 56353] {aka 2410018J24Rik, DEDAF, YEAF1}, Suz12 (SUZ12 polycomb repressive complex 2 subunit) [NCBI Gene 52615] {aka 2610028O16Rik, D11Ertd530e, mKIAA0160}, H3c7 (H3 clustered histone 7) [NCBI Gene 260423] {aka H3.2-221, H3c13, H3c14, H3c15, H3c2, H3c3}, RNF20 (ring finger protein 20) [NCBI Gene 56254] {aka BRE1, BRE1A, hBRE1}, Jarid2 (Jumonji, AT rich interactive domain 2) [NCBI Gene 39103] {aka CG3654, Dmel\CG3654, dJARID2, dJmj, djmj, l(3)j2B8}, H2ax (H2A.X variant histone) [NCBI Gene 15270] {aka H2A.X, H2afx, Hist5-2ax, gammaH2ax}, H2az1 (H2A.Z variant histone 1) [NCBI Gene 51788] {aka H2A.Z, H2A.Z1, H2a.z-1, H2afz}, Pole4 (polymerase (DNA-directed), epsilon 4 (p12 subunit)) [NCBI Gene 66979] {aka 2400007P05Rik, 5830430F06Rik}, His2Av (Histone H2A variant) [NCBI Gene 43229] {aka *i H2av, 5499, CG5499, Dmel\CG5499, H2A, H2A.F/Z}, Prc1 (protein regulator of cytokinesis 1) [NCBI Gene 233406] {aka D7Ertd348e}, H2AC18 (H2A clustered histone 18) [NCBI Gene 8337] {aka H2A, H2A.2, H2A/O, H2A/q, H2AFO, H2a-615}, RNF2 (ring finger protein 2) [NCBI Gene 6045] {aka BAP-1, BAP1, DING, HIPI3, LUSYAM, RING1B}, Jarid2 (jumonji and AT-rich interaction domain containing 2) [NCBI Gene 16468] {aka Jmj, jumonji}, Cbx1 (chromobox 1) [NCBI Gene 12412] {aka Cbx, Cbx-rs2, E430007M08Rik, HP1B, Hp1beta, M31}, H2AZ1 (H2A.Z variant histone 1) [NCBI Gene 3015] {aka H2A.Z-1, H2A.z, H2A/z, H2AFZ, H2AZ}, Atp6ap2 (ATPase, H+ transporting, lysosomal accessory protein 2) [NCBI Gene 70495] {aka (P)RR, 5730403E06Rik, APT6M8-9, ATP6M8-9, Atp6ip2, M8-9} - **Diseases:** RPM (MESH:D004410) - **Chemicals:** Puromycin (MESH:D011691), SDS (MESH:D012967), IGEPAL CA-630 (MESH:C010615), TPL (MESH:C001899), Glutamax (MESH:C054122), EDTA (MESH:D004492), DMSO (MESH:D004121), Oligonucleotides (MESH:D009841), Triton X-100 (MESH:D017830), Alexa Fluor 488 (MESH:C000711379), PBS (MESH:D007854), Copper sulfate (MESH:D019327), NaCl (MESH:D012965), 2-Mercaptoethanol (MESH:D008623), TE (MESH:D013691), 5-ethynyl-2'-deoxyuridine (MESH:C031086), water (MESH:D014867), 1X (-), S (MESH:D013455), KHCO3 (MESH:C026329), LiCl (MESH:D018021), Formaldehyde (MESH:D005557), nitrogen (MESH:D009584), amino acids (MESH:D000596), glycerol (MESH:D005990), Agarose (MESH:D012685), glycine (MESH:D005998), Penicillin (MESH:D010406), IAA (MESH:C030737), pepstatin (MESH:C031375), leupeptin (MESH:C032854), EGTA (MESH:D004533), CO2 (MESH:D002245), N/A (MESH:D012964), Biotin (MESH:D001710), Lipofectamine (MESH:C086724), Sodium ascorbate (MESH:D001205), dTAG (MESH:C030192), Auxin (MESH:D007210), NaOH (MESH:D012972), sodium deoxycholate (MESH:D003840), EdU (MESH:C022811), Streptomycin (MESH:D013307), Tween 20 (MESH:D011136), HCl (MESH:D006851) - **Species:** Drosophila melanogaster (fruit fly, species) [taxon 7227], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Homo sapiens (human, species) [taxon 9606], Bos taurus (bovine, species) [taxon 9913], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Mus musculus (house mouse, species) [taxon 10090], Mycoplasma (genus) [taxon 2093] - **Mutations:** S3D, S2H, 2X, S3E, 1X, M3, 3A, S7C, D1, S7E, H3, 1 M, S1E, 2A, G2, 7 C, T1, G1, S7E, S7, 7 C, S7C, D2, S7, V2, 2X, G2, S2 - **Cell lines:** S2M — Homo sapiens (Human), Transformed cell line (CVCL_E830), -2A — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_A628), E14 — Mus musculus (Mouse), Embryonic stem cell (CVCL_C320), S2E — Mus musculus (Mouse), Hybridoma (CVCL_C5DX), S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232), Pola1-3A — Rattus norvegicus (Rat), Adenocarcinoma of the rat prostate, Cancer cell line (CVCL_3570), MCM2-2A — Canis lupus familiaris (Dog), Canine mammary carcinoma, Cancer cell line (CVCL_L365), S2B — Homo sapiens (Human), Childhood T acute lymphoblastic leukemia, Cancer cell line (CVCL_1860), ELD — Homo sapiens (Human), Adult acute monocytic leukemia, Cancer cell line (CVCL_VN20), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), mES — Homo sapiens (Human), Pleural malignant mesothelioma, Cancer cell line (CVCL_H665), mESCs — Homo sapiens (Human), Embryonic stem cell (CVCL_UI95), H4K20me0 — Mus musculus (Mouse), Hybridoma (CVCL_A9R9), HCT116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC9994263/full.md ## Figures 15 figures with captions in the complete paper: https://tomesphere.com/paper/PMC9994263/full.md ## References 82 references — full list in the complete paper: https://tomesphere.com/paper/PMC9994263/full.md --- Source: https://tomesphere.com/paper/PMC9994263