Details for: H2BC9

Gene ID: 8345

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: H2BC9

Ensembl ID: ENSG00000275713

Description: H2B clustered histone 9

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • precursor B cell CL0000817
    CSI 4.28
    rCSI 3.75%
    PRS 98.1
  • immature B cell CL0000816
    CSI 4.08
    rCSI 3.03%
    PRS 98.69
  • pro-B cell CL0000826
    CSI 3.83
    rCSI 3.18%
    PRS 97.33
  • plasmablast CL0000980
    CSI 3.64
    rCSI 2.86%
    PRS 96.95
  • intestine goblet cell CL0019031
    CSI 2.92
    rCSI 2.59%
    PRS 95.15
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.89
    rCSI 2.61%
    PRS 96.3
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.84
    rCSI 3.28%
    PRS 91.99
  • erythrocyte CL0000232
    CSI 2.82
    rCSI 6.41%
    PRS 94.98
  • megakaryocyte CL0000556
    CSI 2.64
    rCSI 11.44%
    PRS 96.06
  • colon epithelial cell CL0011108
    CSI 2.61
    rCSI 2.73%
    PRS 95.27
  • fraction A pre-pro B cell CL0002045
    CSI 2.56
    rCSI 2.93%
    PRS 98.14
  • BEST4+ enteroycte CL4030026
    CSI 2.55
    rCSI 3.17%
    PRS 95.82
  • colonocyte CL1000347
    CSI 1.91
    rCSI 2.73%
    PRS 95.11
  • large pre-B-II cell CL0000957
    CSI 1.34
    rCSI 3.82%
    PRS 95.62
  • platelet CL0000233
    CSI 1.08
    rCSI 4.5%
    PRS 93.26

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.

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 cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

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 cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
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.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

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

## Summary [H2BC9](/details-gene/8345) (H2B Clustered Histone 9) is a protein-coding gene located on chromosome 6p22.2. It encodes a replication-dependent core histone, H2B type 1-H, which is a fundamental component of the nucleosome. As a structural constituent of chromatin, [H2BC9](/details-gene/8345) plays an essential role in packaging DNA, regulating gene expression, and maintaining genomic stability through processes such as DNA replication and repair. Its function is modulated by numerous post-translational modifications (PTMs), including ubiquitination and phosphorylation, which are critical for transcriptional regulation and cellular responses to stress [Link](https://doi.org/10.1016/j.molcel.2005.09.025), [Link](https://doi.org/10.1016/s0092-8674(03)00355-6). **Overall**, expression data reveals that [H2BC9](/details-gene/8345) is a highly significant marker in rapidly proliferating cells, particularly within the B lymphocyte lineage, including [precursor B cells](/details-cell/CL0000817) and [immature B cells](/details-cell/CL0000816), as well as in other high-turnover tissues like the intestinal epithelium. ## Cellular Roles and Expression Landscape The expression profile of [H2BC9](/details-gene/8345) underscores its critical role in cell proliferation and development. **Overall**, the gene shows the highest significance in cells of the B lymphocyte lineage, with top CSI scores observed in [precursor B cell](/details-cell/CL0000817) (CSI: 4.28), [immature B cell](/details-cell/CL0000816) (CSI: 4.08), and [pro-B cell](/details-cell/CL0000826) (CSI: 3.83). This strong association suggests that robust expression of [H2BC9](/details-gene/8345) is necessary to support the extensive DNA replication and chromatin remodeling required during B cell maturation. Beyond the adaptive immune system, [H2BC9](/details-gene/8345) is also a significant marker for other highly proliferative cell types. These include hematopoietic progenitors like [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 2.89) and their differentiated progeny such as [erythrocyte](/details-cell/CL0000232) (CSI: 2.82) and [megakaryocyte](/details-cell/CL0000556) (CSI: 2.64). Furthermore, its high significance in epithelial cells of the gut, such as [intestine goblet cell](/details-cell/CL0019031) (CSI: 2.92) and [colon epithelial cell](/details-cell/CL0011108) (CSI: 2.61), is consistent with the continuous self-renewal of this tissue. The common feature across these diverse cell types is a high rate of cell division, highlighting the gene's fundamental function in processes coupled to the cell cycle. ## Pathways and Molecular Function The molecular functions of [H2BC9](/details-gene/8345) are central to DNA metabolism and chromatin dynamics. Gene Ontology annotations confirm its primary roles as a '[Structural constituent of chromatin (GO:0030527)](https://www.ebi.ac.uk/QuickGO/term/GO:0030527)' involved in '[Nucleosome assembly (GO:0006334)](https://www.ebi.ac.uk/QuickGO/term/GO:0006334)'. The protein's ability to engage in '[Dna binding (GO:0003677)](https://www.ebi.ac.uk/QuickGO/term/GO:0003677)' and '[Protein heterodimerization activity (GO:0046982)](https://www.ebi.ac.uk/QuickGO/term/GO:0046982)' (primarily with histone H2A) is the basis for nucleosome formation. Reactome pathway analysis reveals the extensive involvement of [H2BC9](/details-gene/8345) in nearly all aspects of nuclear function. Its role is fundamental to core processes such as '[Cell cycle (R-HSA-1640170)](https://reactome.org/content/detail/R-HSA-1640170)', '[Dna replication (R-HSA-69306)](https://reactome.org/content/detail/R-HSA-69306)', and '[Dna repair (R-HSA-73894)](https://reactome.org/content/detail/R-HSA-73894)', which explains its high expression in proliferating cells. Moreover, [H2BC9](/details-gene/8345) is a key substrate in epigenetic regulation, as shown by its participation in pathways like '[Chromatin modifying enzymes (R-HSA-3247509)](https://reactome.org/content/detail/R-HSA-3247509)' and '[Epigenetic regulation of gene expression (R-HSA-212165)](https://reactome.org/content/detail/R-HSA-212165)'. Research has demonstrated that post-translational modifications, such as monoubiquitination, are crucial for regulating transcriptional elongation and developmental gene programs like HOX gene expression [Link](https://doi.org/10.1016/j.cell.2006.04.029), [Link](https://doi.org/10.1016/j.molcel.2005.09.025). This regulatory layer connects the structural role of [H2BC9](/details-gene/8345) to cell-specific transcriptional outcomes, including pathways like '[Transcriptional regulation by runx1 (R-HSA-8878171)](https://reactome.org/content/detail/R-HSA-8878171)', which is critical for hematopoietic stem cell differentiation. ## Research Directions The widespread and fundamental role of [H2BC9](/details-gene/8345) in chromatin biology, coupled with its pronounced expression in specific proliferating cell lineages, suggests several avenues for future research. **Proposed Hypotheses:** 1. Given its high significance in B cell precursors and its role as a hub for epigenetic modifications, it is hypothesized that the landscape of [H2BC9](/details-gene/8345) post-translational modifications (PTMs) dynamically changes during B cell development. Aberrant PTM patterns on [H2BC9](/details-gene/8345) may serve as early markers or drivers of transformation in B-cell malignancies by disrupting normal differentiation programs. 2. The high expression of [H2BC9](/details-gene/8345) in the intestinal epithelium suggests a critical function in maintaining genomic integrity in this high-turnover tissue. It is hypothesized that reduced expression or impaired PTM signaling involving [H2BC9](/details-gene/8345) compromises DNA damage repair efficiency in colonocytes, thereby increasing susceptibility to mutations that can initiate colorectal cancer. **Experimental Approach:** To test the first hypothesis, a combination of proteomics and functional genomics could be employed. Primary human hematopoietic stem cells would be differentiated *in vitro* towards the B cell lineage. Cells would be harvested at distinct developmental stages ([pro-B cell](/details-cell/CL0000826), [precursor B cell](/details-cell/CL0000817), [immature B cell](/details-cell/CL0000816)). [H2BC9](/details-gene/8345) and its modifications would be profiled at each stage using high-resolution mass spectrometry. In parallel, CRISPR-Cas9 could be used to introduce point mutations at key modification sites (e.g., lysine residues targeted for ubiquitination) in a B-cell progenitor line. The impact of these mutations on B cell differentiation, proliferation, and response to DNA damage would be assessed via flow cytometry, RNA-seq, and functional assays. **Therapeutic Potential:** Directly targeting a core histone like [H2BC9](/details-gene/8345) is likely not a viable therapeutic strategy due to its ubiquitous and essential nature, which would lead to severe toxicity. However, its state is controlled by a host of "writer," "reader," and "eraser" enzymes that place, recognize, and remove its post-translational modifications. These enzymes represent highly attractive drug targets. For instance, inhibitors of specific histone ubiquitin ligases (e.g., MSL2 [Link](https://doi.org/10.1016/j.molcel.2011.05.015)) or deubiquitinases (e.g., USP49 [Link](https://doi.org/10.1101/gad.211037.112)) that act on [H2BC9](/details-gene/8345) could be developed. Such a strategy would be one of **inhibition**, aiming to selectively disrupt the epigenetic programs that drive hyper-proliferation in cancers with high [H2BC9](/details-gene/8345) turnover, such as B-cell leukemias and lymphomas.

Genular Protein ID: 2982561975

Symbol: H2B1H_HUMAN

Name: Histone H2B type 1-H

UniProtKB Accession Codes:

Q93079 B2R541 Q4VB74

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 EMDB 1 Ensembl 1 GO 13 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 Pumba 1 RNAct 1 Reactome 48 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9119399

Title: Human histone gene organization: nonregular arrangement within a large cluster.

PubMed ID: 9119399

DOI: 10.1006/geno.1996.4592

PubMed ID: 12408966

Title: The human and mouse replication-dependent histone genes.

PubMed ID: 12408966

DOI: 10.1016/s0888-7543(02)96850-3

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 16627869

Title: Quantitative proteomic analysis of post-translational modifications of human histones.

PubMed ID: 16627869

DOI: 10.1074/mcp.m600007-mcp200

PubMed ID: 12757711

Title: Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase.

PubMed ID: 12757711

DOI: 10.1016/s0092-8674(03)00355-6

PubMed ID: 16307923

Title: Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation.

PubMed ID: 16307923

DOI: 10.1016/j.molcel.2005.09.025

PubMed ID: 16283522

Title: Inhibition of core histones acetylation by carcinogenic nickel(II).

PubMed ID: 16283522

DOI: 10.1007/s11010-005-8285-1

PubMed ID: 16713563

Title: Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II.

PubMed ID: 16713563

DOI: 10.1016/j.cell.2006.04.029

PubMed ID: 16457587

Title: Gene-specific characterization of human histone H2B by electron capture dissociation.

PubMed ID: 16457587

DOI: 10.1021/pr050268v

PubMed ID: 21925322

Title: Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification.

PubMed ID: 21925322

DOI: 10.1016/j.cell.2011.08.008

PubMed ID: 21726816

Title: The RING finger protein MSL2 in the MOF complex is an E3 ubiquitin ligase for H2B K34 and is involved in crosstalk with H3 K4 and K79 methylation.

PubMed ID: 21726816

DOI: 10.1016/j.molcel.2011.05.015

PubMed ID: 22389435

Title: Lysine succinylation and lysine malonylation in histones.

PubMed ID: 22389435

DOI: 10.1074/mcp.m111.015875

PubMed ID: 23824326

Title: USP49 deubiquitinates histone H2B and regulates cotranscriptional pre-mRNA splicing.

PubMed ID: 23824326

DOI: 10.1101/gad.211037.112

PubMed ID: 24681537

Title: Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark.

PubMed ID: 24681537

DOI: 10.1038/nchembio.1497

PubMed ID: 26479788

Title: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.

PubMed ID: 26479788

DOI: 10.1038/ni.3279

PubMed ID: 27105113

Title: Dynamic competing histone H4 K5K8 acetylation and butyrylation are hallmarks of highly active gene promoters.

PubMed ID: 27105113

DOI: 10.1016/j.molcel.2016.03.014

PubMed ID: 27105115

Title: Metabolic regulation of gene expression by histone lysine beta-hydroxybutyrylation.

PubMed ID: 27105115

DOI: 10.1016/j.molcel.2016.03.036

PubMed ID: 31542297

Title: Glutarylation of histone H4 lysine 91 regulates chromatin dynamics.

PubMed ID: 31542297

DOI: 10.1016/j.molcel.2019.08.018

PubMed ID: 31645732

Title: Metabolic regulation of gene expression by histone lactylation.

PubMed ID: 31645732

DOI: 10.1038/s41586-019-1678-1

PubMed ID: 34874266

Title: Serine ADP-ribosylation marks nucleosomes for ALC1-dependent chromatin remodeling.

PubMed ID: 34874266

DOI: 10.7554/elife.71502

Sequence Information:

  • Length: 126
  • Mass: 13892
  • Checksum: FAE0F79FF4BF703D
  • Sequence:
    • MPDPAKSAPA PKKGSKKAVT KAQKKDGKKR KRSRKESYSV YVYKVLKQVH PDTGISSKAM 
GIMNSFVNDI FERIAGEASR LAHYNKRSTI TSREIQTAVR LLLPGELAKH AVSEGTKAVT 
KYTSSK