HMBOX1

Description

The HMBOX1 (homeobox containing 1) is a protein-coding gene located on chromosome 8.

Homeobox containing 1, also known as homeobox telomere-binding protein 1 (HOT1), is a protein that in humans is encoded by the HMBOX1 gene. HMBOX1 directly binds to the double-stranded repeat sequence of telomeres. 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' technique PICh (Proteomics of Isolated Chromatin segments). Subsequently, direct binding to telomeric DNA was demonstrated through a co-crystal structure of the DNA-binding domain 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 and ChIP-seq see little to no such effect at least in several cancer cell lines.

HMBOX1 binds directly to the 5'-TTAGGG-3' repeats in telomeric DNA. It associates with the telomerase complex at sites of active telomere processing and positively regulates telomere elongation. It is important for TERT binding to chromatin, indicating a role in recruitment of the telomerase complex to telomeres. HMBOX1 also plays a role in the alternative lengthening of telomeres (ALT) pathway in telomerase-negative cells where it promotes formation and/or maintenance of ALT-associated promyelocytic leukemia bodies (APBs). It enhances formation of telomere C-circles in ALT cells, suggesting a possible role in telomere recombination. HMBOX1 might also be involved in the DNA damage response at telomeres.

HMBOX1 is also known as HNF1LA, HOT1, PBHNF, TAH1.

Associated Diseases

WES Whole Exome Sequencing