Details for: H2BC17

Gene ID: 8348

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: H2BC17

Ensembl ID: ENSG00000274641

Description: H2B clustered histone 17

Cell Significance Landscape

Associated with

Significant Cells

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

  • megakaryocyte CL0000556
    CSI 3.48
    rCSI 15.08%
    PRS 99.97

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

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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.

## Summary [H2BC17](/details-gene/8348), also known as H2B clustered histone 17, is a protein-coding gene located on chromosome 6p22.1. It encodes a replication-dependent core histone, H2B, which is a fundamental component of the nucleosome. Alongside histones H2A, H3, and H4, it plays a central role in packaging DNA into chromatin, thereby regulating DNA replication, repair, and transcription. **Overall**, expression data indicates that [H2BC17](/details-gene/8348) is a gene of particularly high significance in [megakaryocytes](/details-cell/CL0000556), which is consistent with the extensive DNA synthesis and chromatin remodeling required for their maturation and polyploidization. Its function is modulated by numerous post-translational modifications, which influence chromatin structure and gene expression programs during development and disease [Link](https://doi.org/10.1016/j.molcel.2005.09.025). ## Cellular Roles and Expression Landscape The expression profile of [H2BC17](/details-gene/8348) underscores its essential role in cellular proliferation and differentiation, processes that require large-scale DNA packaging. **Overall**, the primary cellular context for [H2BC17](/details-gene/8348) significance is within the hematopoietic system, specifically in [megakaryocytes](/details-cell/CL0000556) (CSI: 3.48). Megakaryocytes are the bone marrow cells responsible for producing blood platelets, a process that involves a unique form of cell division called endoreduplication, where the cell undergoes multiple rounds of DNA replication without cytokinesis. The high significance of [H2BC17](/details-gene/8348) in these cells is strongly suggestive of its critical function in supplying the histone proteins necessary to package the massively amplified genome, which can reach up to 128N in mature cells. ## Pathways and Molecular Function Functionally, [H2BC17](/details-gene/8348) is integral to the most fundamental nuclear processes. Gene Ontology annotations confirm its role as a [Structural constituent of chromatin](/details-go/GO:0030527) involved in [Nucleosome assembly](/details-go/GO:0006334). It physically resides within the [Nucleosome](/details-go/GO:0000786) and carries out its function through [Dna binding](/details-go/GO:0003677) and [Protein heterodimerization activity](/details-go/GO:0046982), primarily with histone H2A. The Reactome pathway database extensively details the gene's involvement in a vast array of cellular events, which can be grouped into several key themes: * **Chromatin Dynamics and DNA Maintenance:** [H2BC17](/details-gene/8348) is a core participant in pathways governing [Chromatin organization](/details-reactome/R-HSA-4839726), [Dna replication](/details-reactome/R-HSA-69306), [Dna repair](/details-reactome/R-HSA-73894), and [Chromosome maintenance](/details-reactome/R-HSA-73886). * **Cell Cycle Regulation:** Its expression and modification are tightly linked to cell cycle progression, as shown by its involvement in [Cell cycle, mitotic](/details-reactome/R-HSA-69278), [M phase](/details-reactome/R-HSA-68886), and critical surveillance mechanisms like [G2/m checkpoints](/details-reactome/R-HSA-69481). * **Transcriptional and Developmental Regulation:** Beyond its structural role, H2B is a hub for epigenetic regulation. It is involved in [Gene expression (transcription)](/details-reactome/R-HSA-74160), [Epigenetic regulation of gene expression](/details-reactome/R-HSA-212165), and key developmental processes such as the [Activation of hox genes during differentiation](/details-reactome/R-HSA-5619507). Notably, it participates in the pathway [Runx1 regulates genes involved in megakaryocyte differentiation and platelet function](/details-reactome/R-HSA-8936459), directly linking its function to its high significance in [megakaryocytes](/details-cell/CL0000556). * **Post-Translational Modifications:** The function of H2B is fine-tuned by a complex code of post-translational modifications. Pathways such as [Protein ubiquitination](/details-reactome/R-HSA-8852135), [Hats acetylate histones](/details-reactome/R-HSA-3214847), and [Hdacs deacetylate histones](/details-reactome/R-HSA-3214815) highlight this regulatory layer. Research has shown that H2B monoubiquitination is crucial for transcriptional elongation and HOX gene regulation [Link](https://doi.org/10.1016/j.cell.2006.04.029). ## Research Directions The specific importance of [H2BC17](/details-gene/8348) in [megakaryocytes](/details-cell/CL0000556) suggests avenues for research into hematopoiesis and related disorders. **Proposed Hypotheses:** 1. Given its high significance in [megakaryocytes](/details-cell/CL0000556), the expression level of [H2BC17](/details-gene/8348) may be a rate-limiting factor for successful endoreduplication. Insufficient supply of H2B could lead to genomic instability or cell cycle arrest during megakaryopoiesis, resulting in impaired platelet production (thrombocytopenia). 2. Specific post-translational modifications on the H2B protein encoded by [H2BC17](/details-gene/8348) may act as a critical switch for the transcriptional programs that drive terminal megakaryocyte differentiation. For example, ubiquitination or acetylation at specific lysine residues could be required to activate key transcription factors like RUNX1 or GATA1. **Experimental Approach:** To test the first hypothesis, an *in vitro* model of megakaryopoiesis using human CD34+ hematopoietic stem and progenitor cells (HSPCs) could be employed. CRISPR interference (CRISPRi) could be used to specifically knockdown the expression of [H2BC17](/details-gene/8348). Following induction of differentiation with thrombopoietin (TPO), the cellular phenotype would be assessed. Key readouts would include flow cytometric analysis of megakaryocyte surface markers (CD41/CD61) and, crucially, DNA content analysis via propidium iodide staining to quantify the ploidy levels of the differentiating cells. A significant reduction in the proportion of high-ploidy (≥8N) cells in the [H2BC17](/details-gene/8348)-knockdown condition compared to controls would provide strong evidence that its expression is essential for megakaryocyte maturation. **Therapeutic Potential:** As a core structural protein, [H2BC17](/details-gene/8348) itself is an unlikely direct therapeutic target due to the high risk of toxicity in all proliferating cells. However, its role in hematopoiesis suggests an indirect therapeutic angle. The enzymes that post-translationally modify histones are well-established drug targets (e.g., HDAC inhibitors in cancer therapy). Characterizing the specific modification patterns on H2B during normal and malignant megakaryopoiesis (e.g., in acute megakaryoblastic leukemia) could identify critical writers, readers, or erasers of these marks. These enzymes could then be targeted for inhibition or activation to correct aberrant differentiation programs, representing a more precise and viable therapeutic strategy.

Genular Protein ID: 4128747431

Symbol: H2B1O_HUMAN

Name: Histone H2B type 1-O

UniProtKB Accession Codes:

P23527 Q3KPI7 Q8TCV6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 GO 8 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 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 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: 1768865

Title: A novel divergently transcribed human histone H2A/H2B gene pair.

PubMed ID: 1768865

DOI: 10.3109/10425179109020799

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: 14574404

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

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

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: 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: 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: 13906
  • Checksum: 041118811BBF6647
  • Sequence:
    • MPDPAKSAPA PKKGSKKAVT KAQKKDGKKR KRSRKESYSI YVYKVLKQVH PDTGISSKAM 
GIMNSFVNDI FERIAGEASR LAHYNKRSTI TSREIQTAVR LLLPGELAKH AVSEGTKAVT 
KYTSSK