H4C6 | ENSG00000274618 | NCBI 8361

Details for: H4C6

Gene ID: 8361

Gene Type: Protein-coding - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: H4C6

Ensembl ID: ENSG00000274618

Description: H4 clustered histone 6

Selected Context(s): Overall

Cell Significance Landscape

Display Count:

Contexts:

	Overall overall
	Basal cell carcinoma MONDO0020804
	Blood UBERON0000178
	Cerebrospinal fluid UBERON0001359
	Healthy PATO0000461

Associated with

Activated pkn1 stimulates transcription of ar (androgen receptor) regulated genes klk2 and klk3
(R-HSA-5625886)
Activation of anterior hox genes in hindbrain development during early embryogenesis
(R-HSA-5617472)
Activation of hox genes during differentiation
(R-HSA-5619507)
Amyloid fiber formation
(R-HSA-977225)
Assembly of the orc complex at the origin of replication
(R-HSA-68616)
Assembly of the pre-replicative complex
(R-HSA-68867)
B-wich complex positively regulates rrna expression
(R-HSA-5250924)
Base-excision repair, ap site formation
(R-HSA-73929)
Base excision repair
(R-HSA-73884)
Cell cycle
(R-HSA-1640170)
Cell cycle, mitotic
(R-HSA-69278)
Cell cycle checkpoints
(R-HSA-69620)
Cellular responses to stimuli
(R-HSA-8953897)
Cellular responses to stress
(R-HSA-2262752)
Cellular senescence
(R-HSA-2559583)
Chromatin modifications during the maternal to zygotic transition (mzt)
(R-HSA-9821002)
Chromatin modifying enzymes
(R-HSA-3247509)
Chromosome maintenance
(R-HSA-73886)
Cleavage of the damaged purine
(R-HSA-110331)
Cleavage of the damaged pyrimidine
(R-HSA-110329)
Condensation of prophase chromosomes
(R-HSA-2299718)
Defective pyroptosis
(R-HSA-9710421)
Deposition of new cenpa-containing nucleosomes at the centromere
(R-HSA-606279)
Depurination
(R-HSA-73927)
Depyrimidination
(R-HSA-73928)
Developmental biology
(R-HSA-1266738)
Disease
(R-HSA-1643685)
Diseases of programmed cell death
(R-HSA-9645723)
Dna damage/telomere stress induced senescence
(R-HSA-2559586)
Dna double-strand break repair
(R-HSA-5693532)
Dna double strand break response
(R-HSA-5693606)
Dna methylation
(R-HSA-5334118)
Dna repair
(R-HSA-73894)
Dna replication
(R-HSA-69306)
Dna replication pre-initiation
(R-HSA-69002)
Epigenetic regulation by wdr5-containing histone modifying complexes
(R-HSA-9917777)
Epigenetic regulation of adipogenesis genes by mll3 and mll4 complexes
(R-HSA-9851695)
Epigenetic regulation of gene expression
(R-HSA-212165)
Epigenetic regulation of gene expression by mll3 and mll4 complexes
(R-HSA-9818564)
Ercc6 (csb) and ehmt2 (g9a) positively regulate rrna expression
(R-HSA-427389)
Esr-mediated signaling
(R-HSA-8939211)
Estrogen-dependent gene expression
(R-HSA-9018519)
Formation of the beta-catenin:tcf transactivating complex
(R-HSA-201722)
G2/m checkpoints
(R-HSA-69481)
G2/m dna damage checkpoint
(R-HSA-69473)
Gene expression (transcription)
(R-HSA-74160)
Generic transcription pathway
(R-HSA-212436)
Gene silencing by rna
(R-HSA-211000)
Hats acetylate histones
(R-HSA-3214847)
Hcmv early events
(R-HSA-9609690)
Hcmv infection
(R-HSA-9609646)
Hcmv late events
(R-HSA-9610379)
Hdacs deacetylate histones
(R-HSA-3214815)
Hdms demethylate histones
(R-HSA-3214842)
Hdr through homologous recombination (hrr) or single strand annealing (ssa)
(R-HSA-5693567)
Homology directed repair
(R-HSA-5693538)
Infectious disease
(R-HSA-5663205)
Inhibition of dna recombination at telomere
(R-HSA-9670095)
Maternal to zygotic transition (mzt)
(R-HSA-9816359)
Meiosis
(R-HSA-1500620)
Meiotic recombination
(R-HSA-912446)
Meiotic synapsis
(R-HSA-1221632)
Metabolism of proteins
(R-HSA-392499)
Mitotic prophase
(R-HSA-68875)
Mll4 and mll3 complexes regulate expression of pparg target genes in adipogenesis and hepatic steatosis
(R-HSA-9841922)
M phase
(R-HSA-68886)
Negative epigenetic regulation of rrna expression
(R-HSA-5250941)
Nonhomologous end-joining (nhej)
(R-HSA-5693571)
Norc negatively regulates rrna expression
(R-HSA-427413)
Oxidative stress induced senescence
(R-HSA-2559580)
Packaging of telomere ends
(R-HSA-171306)
Pkmts methylate histone lysines
(R-HSA-3214841)
Positive epigenetic regulation of rrna expression
(R-HSA-5250913)
Post-translational protein modification
(R-HSA-597592)
Prc2 methylates histones and dna
(R-HSA-212300)
Pre-notch expression and processing
(R-HSA-1912422)
Pre-notch transcription and translation
(R-HSA-1912408)
Processing of dna double-strand break ends
(R-HSA-5693607)
Recognition and association of dna glycosylase with site containing an affected purine
(R-HSA-110330)
Recognition and association of dna glycosylase with site containing an affected pyrimidine
(R-HSA-110328)
Recruitment and atm-mediated phosphorylation of repair and signaling proteins at dna double strand breaks
(R-HSA-5693565)
Regulation of endogenous retroelements
(R-HSA-9842860)
Regulation of endogenous retroelements by krab-zfp proteins
(R-HSA-9843940)
Regulation of endogenous retroelements by piwi-interacting rnas (pirnas)
(R-HSA-9845323)
Regulation of endogenous retroelements by the human silencing hub (hush) complex
(R-HSA-9843970)
Replacement of protamines by nucleosomes in the male pronucleus
(R-HSA-9821993)
Reproduction
(R-HSA-1474165)
Rho gtpase effectors
(R-HSA-195258)
Rho gtpases activate pkns
(R-HSA-5625740)
Rmts methylate histone arginines
(R-HSA-3214858)
Rna polymerase ii transcription
(R-HSA-73857)
Rna polymerase i promoter clearance
(R-HSA-73854)
Rna polymerase i promoter escape
(R-HSA-73772)
Rna polymerase i promoter opening
(R-HSA-73728)
Rna polymerase i transcription
(R-HSA-73864)
Runx1 regulates genes involved in megakaryocyte differentiation and platelet function
(R-HSA-8936459)
Runx1 regulates transcription of genes involved in differentiation of hscs
(R-HSA-8939236)
Senescence-associated secretory phenotype (sasp)
(R-HSA-2559582)
Signaling by notch
(R-HSA-157118)
Signaling by nuclear receptors
(R-HSA-9006931)
Signaling by rho gtpases
(R-HSA-194315)
Signaling by rho gtpases, miro gtpases and rhobtb3
(R-HSA-9716542)
Signaling by wnt
(R-HSA-195721)
Signal transduction
(R-HSA-162582)
Sirt1 negatively regulates rrna expression
(R-HSA-427359)
Sumo e3 ligases sumoylate target proteins
(R-HSA-3108232)
Sumoylation
(R-HSA-2990846)
Sumoylation of chromatin organization proteins
(R-HSA-4551638)
Tcf dependent signaling in response to wnt
(R-HSA-201681)
Telomere maintenance
(R-HSA-157579)
Transcriptional regulation by runx1
(R-HSA-8878171)
Transcriptional regulation by small rnas
(R-HSA-5578749)
Transcriptional regulation of granulopoiesis
(R-HSA-9616222)
Viral infection pathways
(R-HSA-9824446)
Cenp-a containing nucleosome
(GO:0043505)
Chromatin organization
(GO:0006325)
Chromosome, telomeric region
(GO:0000781)
Dna binding
(GO:0003677)
Extracellular exosome
(GO:0070062)
Extracellular region
(GO:0005576)
Membrane
(GO:0016020)
Negative regulation of megakaryocyte differentiation
(GO:0045653)
Nucleoplasm
(GO:0005654)
Nucleosome
(GO:0000786)
Nucleosome assembly
(GO:0006334)
Nucleus
(GO:0005634)
Protein-containing complex
(GO:0032991)
Protein binding
(GO:0005515)
Protein heterodimerization activity
(GO:0046982)
Protein localization to cenp-a containing chromatin
(GO:0061644)
Rna binding
(GO:0003723)
Structural constituent of chromatin
(GO:0030527)
Telomere organization
(GO:0032200)

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

erythrocyte CL0000232

CSI 2.98

rCSI 6.75%

PRS 99.07
basal cell of epidermis CL0002187

CSI 1.8

rCSI 3.2%

PRS 91.33
large pre-B-II cell CL0000957

CSI 1.64

rCSI 4.67%

PRS 99.2

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

Description

## Summary [H4C6](/details-gene/8361), also known as H4 Clustered Histone 6, is a protein-coding gene located on chromosome 6p22.2. As a member of the core histone family, [H4C6](/details-gene/8361) is a fundamental component of the nucleosome, playing a critical role in packaging DNA into chromatin. Its primary functions are linked to [chromatin organization](/details-cell/GO:0006325), [nucleosome assembly](/details-cell/GO:0006334), and DNA binding, making it essential for genome stability, gene regulation, DNA replication, and repair. **Overall**, expression data indicates its highest significance in terminally differentiating cells like [erythrocytes](/details-cell/CL0000232) and in highly proliferative tissues such as the [basal cell of epidermis](/details-cell/CL0002187) and developing [large pre-B-II cells](/details-cell/CL0000957), underscoring its essential role in processes involving extensive cell division and chromatin remodeling. ## Cellular Roles and Expression Landscape The expression profile of [H4C6](/details-gene/8361) highlights its importance in cells undergoing significant proliferation, differentiation, or chromatin restructuring. **Overall**, the gene shows the highest significance in [erythrocytes](/details-cell/CL0000232) (CSI: 2.98), which are cells that undergo extreme chromatin condensation during their final stages of maturation. This suggests a potentially crucial role for [H4C6](/details-gene/8361) in organizing the genome prior to nuclear expulsion in erythropoiesis. High significance is also observed in progenitor and stem cell populations known for their high turnover rate. This includes [basal cell of epidermis](/details-cell/CL0002187) (CSI: 1.80), the proliferative layer responsible for skin regeneration, and [large pre-B-II cell](/details-cell/CL0000957) (CSI: 1.64), a rapidly dividing precursor in the B-lymphocyte lineage. This pattern is consistent with the fundamental role of histone proteins in replicating chromosomes and re-establishing chromatin structure after cell division. The collective data suggest that [H4C6](/details-gene/8361) is not merely a ubiquitous housekeeping gene but is particularly integral to the biological programs of highly dynamic cell populations. ## Pathways and Molecular Function [H4C6](/details-gene/8361) functions as a [structural constituent of chromatin](/details-cell/GO:0030527) and is a central player in a vast number of fundamental cellular processes related to genome maintenance. Its molecular functions include [DNA binding](/details-cell/GO:0003677) and [protein heterodimerization activity](/details-cell/GO:0046982), which are essential for forming the octameric histone core of the [nucleosome](/details-cell/GO:0000786). Consistent with its role in cell proliferation, [H4C6](/details-gene/8361) is implicated in numerous Reactome pathways governing the [Cell cycle](/details-cell/R-HSA-1640170), including [DNA replication](/details-cell/R-HSA-69306) and progression through [M phase](/details-cell/R-HSA-68886). Furthermore, it is deeply involved in pathways of [DNA repair](/details-cell/R-HSA-73894), such as [Base excision repair](/details-cell/R-HSA-73884) and [DNA double strand break response](/details-cell/R-HSA-5693606), highlighting its importance in maintaining genomic integrity. The gene's involvement is also noted in broader biological themes like [Developmental biology](/details-cell/R-HSA-1266738) and [Gene expression (transcription)](/details-cell/R-HSA-74160), reflecting the universal requirement of chromatin modulation for regulating cellular programs. The gene is also annotated to biological processes such as [Negative regulation of megakaryocyte differentiation](/details-cell/GO:0045653), indicating a specific regulatory role in hematopoietic lineage decisions. ## Research Directions The expression profile and functional annotations of [H4C6](/details-gene/8361) suggest it is a critical component of cellular processes involving high rates of division and significant chromatin remodeling. This provides a foundation for several testable hypotheses. 1. **Hypothesis:** The high significance of [H4C6](/details-gene/8361) in [erythrocytes](/details-cell/CL0000232) suggests it is essential for the terminal stages of erythropoiesis, specifically for the dramatic chromatin condensation required for nuclear expulsion. Perturbation of [H4C6](/details-gene/8361) levels would therefore impair or block the formation of mature, enucleated red blood cells. 2. **Hypothesis:** Based on its annotation in [Negative regulation of megakaryocyte differentiation](/details-cell/GO:0045653), [H4C6](/details-gene/8361) may function as a molecular gatekeeper at the megakaryocyte-erythroid progenitor stage. Its sustained expression could favor the erythroid fate, and its downregulation may be a prerequisite for commitment to the megakaryocyte lineage, which involves a distinct process of endoreduplication rather than standard mitosis. **Experimental Approach:** To test the first hypothesis, an *in vitro* model of human erythroid differentiation using CD34+ hematopoietic stem and progenitor cells could be employed. [H4C6](/details-gene/8361) expression could be suppressed using a lentiviral-based shRNA or CRISPR interference (CRISPRi) system. The impact on differentiation would be assessed by monitoring cell morphology, quantifying the rate of enucleation via imaging flow cytometry using a nuclear stain like Hoechst 33342, and analyzing the expression of terminal erythroid markers such as Glycophorin A (CD235a). A significant reduction in the percentage of enucleated cells in the [H4C6](/details-gene/8361)-knockdown condition compared to controls would support its critical role in the final maturation of erythrocytes. **Therapeutic Potential:** As a core histone protein, [H4C6](/details-gene/8361) is an exceptionally poor candidate for direct therapeutic targeting due to its ubiquitous expression and essential role in all nucleated cells, which would likely lead to profound, non-specific toxicity. However, the enzymes that post-translationally modify histones ("writers" and "erasers") are established drug targets. A deeper understanding of the specific modification patterns on [H4C6](/details-gene/8361) in pathological contexts, such as hematological malignancies or other hyperproliferative disorders, could unveil novel strategies for targeting these modifying enzymes to indirectly modulate chromatin function with greater specificity.

Disclaimer: This in-silico analysis is generated by an AI language model and may contain inaccuracies or hallucinations. However, it is cross-referenced with curated gene expression data from major biological sources. Please verify the information before use.