Homeobox containing 1, also known as homeobox telomere-binding protein 1 (HOT1), is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the HMBOX1 gene. HMBOX1 directly binds to the double-stranded repeat sequence of

telomere A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...

s. HMBOX1 has originally been identified to associate with telomeric chromatin in telomerase-positive cancer cells and cancer cells that maintain their telomeres based on the Alternative Lengthening of Telomeres (ALT) mechanism by the 'reverse

ChIP Chromatin immunoprecipitation (ChIP) is a type of immunoprecipitation experimental technique used to investigate the interaction between proteins and DNA in the cell. It aims to determine whether specific proteins are associated with specific genomi ...

' technique PICh (Proteomics of Isolated Chromatin segments). Subsequently, direct binding to telomeric DNA was demonstrated through a co-

crystal structure In crystallography, crystal structure is a description of the ordered arrangement of atoms, ions or molecules in a crystal, crystalline material. Ordered structures occur from the intrinsic nature of the constituent particles to form symmetric pat ...

of the

DNA-binding domain A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a genera ...

of HMBOX1 with telomeric DNA. Loss-of-function and gain-of-function experiments classify HMBOX1 as a positive regulator of telomere length. HMBOX1 had originally been described as a transcriptional repressor based on reporter gene assays, but genome-wide approaches using

RNA-seq RNA-Seq (named as an abbreviation of RNA sequencing) is a sequencing technique which uses next-generation sequencing (NGS) to reveal the presence and quantity of RNA in a biological sample at a given moment, analyzing the continuously changing c ...

and

ChIP-seq ChIP-sequencing, also known as ChIP-seq, is a method used to analyze protein interactions with DNA. ChIP-seq combines chromatin immunoprecipitation (ChIP) with Massively parallel signature sequencing, massively parallel DNA sequencing to identify t ...

see little to no such effect at least in several cancer cell lines.

References

Further reading