Biology subjects

Soman, A.

Publications and source records attributed to Soman, A..

4 recordsLinked to original sources

bioRxiv2026

HOT1 functions as a homodimer to promote ALT-permissive chromatin

Telomere homeostasis is a tightly regulated and dynamic process sustained by a network of proteins that organize telomeric chromatin and safeguard chromosome stability. In ALT-positive cells, telomere maintenance relies on recombination-based mechanisms and is modulated by local chromatin states and epigenetic regulation. Here, we show that the telomeric binding protein HOT1 (HMBOX1) requires dimerization - depending both on interaction with the dimerization-mediators DYNLL1/2 and its intrinsic HNFp1 domain - for its stable association with telomeres in vivo. Loss of HOT1 leads to an epigenetic switch from H3K9acK14ac to H3K9me3 at telomeres accompanied by attenuated ALT activity as illustrated by reduced ALT recombination by-products (C-circles) and a decrease in telomere dysfunction-induced foci (TIFs). We further show via binding assays and cross-linking mass spectrometry (XL-MS) analyses that HOT1 directly interacts with telomeric nucleosomes, providing a molecular basis for its involvement in telomeric chromatin organization. Collectively, these findings suggest that HOT1 functions as a homodimer to promote a telomeric chromatin state that is highly permissive for ALT recombination.

cell biology↗

bioRxiv2025

SMCHD1 compacts DNA directly in an ATP-regulated manner

Structural maintenance of chromosome (SMC) complexes play crucial roles in genome organization by DNA loop extrusion. SMCHD1 is a non-canonical SMC protein important for X-inactivation, imprinting and the silencing of specific autosomal genes. While it is known to be a repressor, little is known about its structure or mechanism of action. Here, we show that the SMCHD1 homodimer is flexible and dynamic in solution. This flexibility is conferred by its yet uncharacterized linker domain, which can alter its length by dynamically switching between compact and extended conformations. Interestingly, we observed that SMCHD1 can directly bridge and compact DNA, independently of other proteins, forming large protein-DNA clusters. SMCHD1 contains a GHKL ATPase domain and SMC hinge domain, however each domain alone is insufficient for DNA compaction. DNA compaction rate decreases when the linker domain is removed. The coiled-coil domain does not affect compaction rate but facilitates interaction with a partner protein LRIF1. Surprisingly, DNA compaction by SMCHD1 does not require ATP and paradoxically, compaction rate is reduced with the addition of ATP. Similarly, SMCHD1 forms clusters with reconstituted nucleosome arrays in the absence of ATP, and the addition of ATP results in a reduction in cluster sizes. Our data provides biophysical and mechanistic insights into the role of SMCHD1 in gene silencing and genome organization.

molecular biology↗

bioRxiv2022

The columnar structure of human telomeric chromatin suggests mechanisms for telomere maintenance

Telomeres, the ends of eukaryotic chromosomes, play pivotal roles in ageing and cancer and are targets of DNA damage and response. However, little is known about the structure and organization of telomeric chromatin at the molecular level. We used electron microscopy and single-molecule magnetic tweezers to characterize well-defined telomeric chromatin fibers of kilobasepair length. The cryo-EM structure of the compact telomeric tetranucleosome revealed a novel columnar folding, unusually short nucleosome repeat length of [~]132bp and the role of the histone N-terminal tails in stabilizing this structure. This is the first near-high resolution structure of chromatin with a native DNA sequence. The columnar structure exposes the DNA, making them susceptible to DNA damage. The telomeric tetranucleosome also exists in an alternative well-defined state, with one nucleosome open, accessible to protein factors. This suggests that protein factors, which plays a role in maintaining telomeres, can bind to telomeric chromatin in its compact heterochromatic form. The features of the telomeric chromatin structure reveals important insights of significant relevance for telomere function in vivo that provides information on mechanisms of nucleosome recognition by chromatin factors

molecular biology↗

bioRxiv2019

The Human Telomeric Nucleosome Displays Distinct Structural and Dynamic Properties

Telomeres protect the ends of our chromosomes and are key to maintaining genomic integrity during cell division and differentiation. However, our knowledge of telomeric chromatin and nucleosome structure at the molecular level is limited. Here, we aimed to define the structure, dynamics as well as properties in solution of the human telomeric nucleosome. We first determined the 2.2 [A] crystal structure of a human telomeric nucleosome core particle (NCP) containing 145 bp DNA, which revealed the same helical path for the DNA as well as symmetric stretching in both halves of the NCP as that of the 145 bp 601 NCP. In solution, the telomeric nucleosome exhibited a less stable and a markedly more dynamic structure compared to NCPs containing DNA positioning sequences. These observations provide molecular insights into how telomeric DNA forms nucleosomes and chromatin and advance our understanding of the unique biological role of telomeres.

biochemistry↗