HOT1 functions as a homodimer to promote ALT-permissive chromatin

HOT1 (HMBOX1) forms a homodimer required for stable telomere association in ALT-positive cells, and its loss shifts telomeric chromatin away from an ALT-permissive state.

• Why it matters: ALT relies on recombination, but how telomeric chromatin states are controlled to permit ALT activity remains unclear, limiting understanding of telomere homeostasis in ALT-positive cells.
• What they did: HOT1 dimerization depends on DYNLL1/2 and its intrinsic HNFp1 domain; the study assessed HOT1–telomere stability in vivo and measured ALT readouts including C-circles and TIFs.
• The result: HOT1 loss triggers an epigenetic switch from H3K9acK14ac to H3K9me3 at telomeres, reduces ALT recombination by-products (C-circles), lowers TIFs, and supports a model where HOT1 directly contacts telomeric nucleosomes via binding assays and XL-MS.

AI summary of the abstract · may contain errors · not medical advice · read the paper.