Disease relevance of HIST1H1C

• The cosmid clone covers 30 kb upstream of the H1.2 gene and overlaps with two phage clones covering the core histone genes and the pseudogene [1].
• The recombinant human histones H1 zero and H1.2 cause different toxicity profiles on the human leukemia cell line K562 [2].
• The human histones H1 zero and H1.2 were expressed in E. coli and purified to homogenity [2].
• METHODS: To characterize the antimicrobial properties of histone H1.2 against potential causative organisms of burn wound infections, the in vitro radial diffusion assay and modified NCCLS microbroth dilution MIC assay were carried out [3].

High impact information on HIST1H1C

• Recent evidence reveals an unexpected role for the linker histone H1.2 in DNA damage-induced apoptosis [4].
• DNA double strand breaks induce translocation of nuclear H1.2 to the cytoplasm, where it promotes release of cytochrome c from mitochondria by activating the Bcl-2 family protein, Bak [4].
• When Gln-54 in Histone H1t was mutated to lysine, its binding affinity towards DNA substrates was comparable to that of histone H1d [5].
• The aim of this study was to investigate the in vitro and in vivo activity of histone H1.2 in infected burn wounds and its potential toxicity [3].
• Surprisingly, histone H1.2 showed cytotoxicity with an LD50 of 7.91 mg/L in primary human keratinocytes [3].

Biological context of HIST1H1C

• Removal of this promoter portion causes in chloramphenicol acetyl transferase reporter gene constructs a loss of the S-phase control function of the H1.2 promoter in HeLa cells [6].
• The allele frequency of these sequence variants in a normal Swedish population was found to be 6.8% for the H1.2 GCC-->GTC shift, indicating that this is a relatively frequent polymorphism [7].
• Addition of a 73-bp rat H1t promoter fragment (-948 to -875, containing the 5' portion of the silencer region) to a site immediately upstream from the histone H1d proximal promoter led to significantly reduced luciferase expression upon transient transfection (56% in C127I cells and 44% in HeLa cells) [8].

Anatomical context of HIST1H1C

• In K562 cells, a homozygous GCC-->GTC shift was found at codon 18, giving rise to H1.2 Ala17Val because the initial methionine is removed in H1 histones [7].
• Histone H1.2, a housekeeping protein that binds nucleosomal linkers, has recently been identified as an apoptogenic factor released from the nucleus to the cytosol in response to double strand DNA breaks [9].

Associations of HIST1H1C with chemical compounds

• In K562 erythroleukemic cells, alanine at position 17 in H1.2 was replaced by valine, and, in Raji B lymphoblastoid cells, lysine at position 173 in H1.4 was replaced by arginine [7].

Physical interactions of HIST1H1C

• This repressive action of H1.2 complex involves direct interaction of H1.2 with p53, which in turn blocks p300-mediated acetylation of chromatin [10].

Regulatory relationships of HIST1H1C

• Role of a distal promoter element in the S-phase control of the human H1.2 histone gene transcription [6].

Other interactions of HIST1H1C

• In contrast to the differential patterns of the other subtypes, H1.2 and H1.4 were in all cells expressed at a high level, indicating a basal function compared with the other H1 histones [11].
• The potent inhibitory activity of histone H1.2 C-terminal fragments on furin [12].
• Enzymes responsible for opening up chromatin, Hmgn3 and Hmgb1, were upregulated whereas enzymes that condense chromatin, histone H1.2, were downregulated [13].

References