H3C4 Gene

Name H3 clustered histone 4
Description Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H3 family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq, Aug 2015]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Histone H3 variants and their post‐translational modifications perform central roles in orchestrating chromatin structure, gene expression, and genome stability. In several pediatric high‐grade gliomas, for example, recurrent missense mutations in genes encoding histone H3.3 and H3.1—most notably the lysine‐to‐methionine substitution at position 27 (K27M) and glycine 34 alterations—disrupt the normal deposition of the repressive H3K27 trimethyl mark by directly inhibiting the enzymatic activity of the Polycomb repressive complex 2. This epigenetic dysregulation has been directly linked to oncogenic transformation ("}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ").\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to these mutation‐driven effects, the proper incorporation of histone H3 variants into chromatin is tightly regulated by dedicated histone chaperones—including DAXX, ATRX, HIRA, and HJURP—that mediate both replication‐independent and centromere‐specific nucleosome assembly. Their activities ensure accurate heterochromatin formation, centromere specification, and maintenance of genome organization ("}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": ").\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Further, specific modifications—such as H3K36 trimethylation on H3.3—are read by specialized proteins like ZMYND11, which couple transcription elongation control to tumor suppression. This function integrates histone variant incorporation with the regulation of gene expression programs important for cellular differentiation and the prevention of malignant transformation ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ").\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, the dynamic interplay among histone modifications, chaperone‐mediated nucleosome assembly, and chromatin remodelers underpins critical processes such as DNA replication and repair. For instance, deposition of variant H3.3 at sites of DNA damage facilitates efficient non‐homologous end joining and overall genomic maintenance ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ").\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies illustrate that histone H3—through its variant forms and associated modifications—functions as a key regulator of chromatin architecture and cellular identity. Disruption of these finely tuned mechanisms, whether by mutation or misregulated deposition, leads to altered epigenetic landscapes that contribute to developmental abnormalities and oncogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Peter W Lewis, Manuel M Müller, Matthew S Koletsky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1232245"}], "href": "https://doi.org/10.1126/science.1232245"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23539183"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23539183"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Dong-Anh Khuong-Quang, Pawel Buczkowicz, Patricia Rakopoulos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00401-012-0998-0"}], "href": "https://doi.org/10.1007/s00401-012-0998-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22661320"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22661320"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sam Behjati, Patrick S Tarpey, Nadège Presneau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2814"}], "href": "https://doi.org/10.1038/ng.2814"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24162739"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24162739"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Pawel Buczkowicz, Christine Hoeman, Patricia Rakopoulos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2936"}], "href": "https://doi.org/10.1038/ng.2936"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24705254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24705254"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Pascal Drané, Khalid Ouararhni, Arnaud Depaux, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.566910"}], "href": "https://doi.org/10.1101/gad.566910"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20504901"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20504901"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Elaine M Dunleavy, Danièle Roche, Hideaki Tagami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HJURP is a cell-cycle-dependent maintenance and deposition factor of CENP-A at centromeres."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2009.02.040"}], "href": "https://doi.org/10.1016/j.cell.2009.02.040"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19410545"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19410545"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Lars E T Jansen, Ben E Black, Daniel R Foltz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Propagation of centromeric chromatin requires exit from mitosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200701066"}], "href": "https://doi.org/10.1083/jcb.200701066"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17339380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17339380"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Meghan C Barnhart, P Henning J L Kuich, Madison E Stellfox, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HJURP is a CENP-A chromatin assembly factor sufficient to form a functional de novo kinetochore."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201012017"}], "href": "https://doi.org/10.1083/jcb.201012017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21768289"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21768289"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Hong Wen, Yuanyuan Li, Yuanxin Xi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature13045"}], "href": "https://doi.org/10.1038/nature13045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24590075"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24590075"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Rui Guo, Lijuan Zheng, Juw Won Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BS69/ZMYND11 reads and connects histone H3.3 lysine 36 trimethylation-decorated chromatin to regulated pre-mRNA processing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2014.08.022"}], "href": "https://doi.org/10.1016/j.molcel.2014.08.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25263594"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25263594"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Martijn S Luijsterburg, Inge de Krijger, Wouter W Wiegant, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PARP1 Links CHD2-Mediated Chromatin Expansion and H3.3 Deposition to DNA Repair by Non-homologous End-Joining."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2016.01.019"}], "href": "https://doi.org/10.1016/j.molcel.2016.01.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26895424"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26895424"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Malgorzata Krajewska, Ruben Dries, Andrew V Grassetti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CDK12 loss in cancer cells affects DNA damage response genes through premature cleavage and polyadenylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-09703-y"}], "href": "https://doi.org/10.1038/s41467-019-09703-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30988284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30988284"}]}]}]}
NCBI Gene ID 8351
API
Download Associations
Predicted Functions View H3C4's ARCHS4 Predicted Functions.
Co-expressed Genes View H3C4's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View H3C4's ARCHS4 Predicted Functions.

Functional Associations

H3C4 has 798 functional associations with biological entities spanning 5 categories (disease, phenotype or trait, chemical, functional term, phrase or reference, cell line, cell type or tissue, gene, protein or microRNA) extracted from 9 datasets.

Click the + buttons to view associations for H3C4 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of H3C4 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
CM4AI KOLF21J CRISPRi Gene Perturbation Atlas gene perturbations changing expression of H3C4 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores 2025 diseases associated with H3C4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with H3C4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of H3C4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of H3C4 gene from the Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures dataset.
Rummagene Transcription Factor Associations 2026 transcription factors regulating expression of H3C4 gene from the Rummagene Transcription Factor Associations 2026 dataset.
Sci-Plex Drug Perturbation Signatures drug perturbations changing expression of H3C4 gene from the Sci-Plex Drug Perturbation Signatures dataset.
WikiPathways Pathways 2024 pathways involving H3C4 protein from the WikiPathways Pathways 2024 dataset.