Molecular Biology Terms Starting With H
Molecular Biology Glossary: H
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Histone Modification
/ HIS-tohn mod-ih-fih-KAY-shun / · Greek: histos (tissue) + Latin: modificare
Histone Modification is the covalent addition or removal of chemical groups, including acetyl, methyl, phosphate, ubiquitin, and SUMO, to specific amino acid residues on histone tail domains, altering chromatin structure and gene expression.
Histone acetyltransferases add acetyl groups to lysine residues, neutralizing their positive charge and loosening chromatin compaction to promote transcription; histone deacetylases reverse this by removing acetyl groups and restoring a more repressive chromatin state. Methylation at different positions carries distinct regulatory meanings: H3K4me3 marks active promoters, H3K27me3 marks Polycomb-repressed genes, and H3K9me3 is associated with constitutive heterochromatin at centromeres and repetitive elements. A single histone tail can carry multiple simultaneous modifications, and the combination of marks, sometimes called the histone code, is read by effector proteins containing specialized domains such as bromodomains, which recognize acetyl-lysine, and chromodomains, which recognize methyl-lysine.
Histone phosphorylation at H3 serine 10 rises sharply during mitosis and is used as a cytological marker of cell division. Dysregulation of histone-modifying enzymes drives many cancers; EZH2, the methyltransferase that deposits H3K27me3, is overexpressed in diffuse large B-cell lymphoma and is the target of the approved drug tazemetostat.
The histone variant H2A.Z, which replaces canonical H2A at thousands of promoters across the genome, is not chemically modified in the same way as standard histones but still shifts nucleosome stability; its incorporation alone reduces the energy needed to unwrap DNA by roughly 2 kilocalories per mole, showing that histone identity itself, not only post-translational modification, shapes chromatin accessibility.
Histones are passive structural spools whose only job is to compact DNA. Histone modifications are read by specific effector proteins that recruit transcriptional activators, repressors, and DNA repair factors, making histones active participants in nearly every process that requires access to the genome.
Polycomb repressive complex 2 deposits H3K27me3 across the four HOX gene clusters in human embryonic stem cells, keeping these developmental regulators silent. As cells differentiate along specific lineages, H3K27me3 is selectively removed from individual HOX loci, and the exposed genes are activated in a pattern that specifies anterior-posterior body axis identity.
Homologous Recombination
/ hoh-MOL-oh-gus ree-kom-bih-NAY-shun / · Greek: homoios (similar) + Latin: recombinare
Homologous Recombination is a high-fidelity DNA repair and exchange pathway that uses a homologous DNA sequence as a template to repair breaks or generate genetic recombination.
The pathway begins when broken DNA ends are resected to create 3-prime single-stranded overhangs that can search for homology. RAD51 coats these overhangs to form a nucleoprotein filament, assisted by BRCA2 in mammalian cells, and promotes strand invasion into an intact homologous duplex. DNA polymerase then extends the invading strand using the intact sequence as a template, after which the joint molecule is resolved to restore continuity.
Homologous recombination is most active in S and G2 phases, when a sister chromatid is available, and defects in BRCA1, BRCA2, PALB2, or RAD51 paralogs compromise repair and increase cancer susceptibility.
BRCA2 is essentially a RAD51-loading factor. Cells lacking functional BRCA2 can form double-strand breaks normally but fail to assemble productive RAD51 filaments, forcing repair toward more error-prone pathways.
Broken DNA is always joined randomly. Homologous recombination copies information from a matching DNA template, making it much more accurate than end joining when an intact sister chromatid is available.
During meiosis in Caenorhabditis elegans, homologous recombination normally produces about 1 crossover per chromosome pair. These 6 crossover-linked bivalents create chiasmata that physically link homologs and help segregate chromosomes accurately into eggs and sperm.
Hybridization
/ hy-brid-ih-ZAY-shun / · Latin: hybrida (mixed offspring) + -ization
Hybridization is the formation of a stable double-stranded nucleic acid duplex between two complementary single-stranded sequences through Watson-Crick base pairing.
Duplex stability depends on base-pair complementarity, strand length, temperature, salt concentration, and the presence of denaturing agents such as formamide. Researchers adjust these stringency conditions to permit only perfectly matched sequences to remain paired, or to tolerate mismatches when detecting related but non-identical sequences. At high stringency, a single mismatched base pair in a 20-nucleotide probe can reduce binding affinity by more than tenfold, giving hybridization-based assays their diagnostic precision.
Southern blotting, fluorescence in situ hybridization, and DNA microarrays all exploit this specificity to detect particular sequences in complex biological samples. A standard diagnostic hybridization probe for detecting a pathogen typically requires at least 15 to 20 consecutive complementary nucleotides to form a stable duplex at physiological salt concentrations.
DNA microarrays used in the Human Genome Project era could simultaneously query more than one million distinct sequences on a chip the size of a postage stamp, each spot containing millions of copies of a single probe sequence. This density was achieved by photolithographic synthesis of oligonucleotides directly on the chip surface, a method developed at Affymetrix in the early 1990s.
Building Blocks of Nucleic Acids →Hybridization means mixing any two DNA samples together. Stable hybridization requires sequences that are complementary or nearly complementary, and mismatches above a threshold determined by stringency conditions will prevent a stable duplex from forming.
Fluorescent in situ hybridization probes designed to detect the BCR-ABL fusion gene in chronic myelogenous leukemia bind to chromosomes 9 and 22 in patient cells. When the translocation is present, two fluorescent signals appear on the same chromosome rather than on separate ones, and cytogeneticists score hundreds of cells per patient sample to quantify the proportion carrying the fusion.