Biology subjects

Soboleva, T.

Publications and source records attributed to Soboleva, T..

3 recordsLinked to original sources

bioRxiv2026

HP1α depletion and TGFβ activation exert antagonistic effects on 3D genome organization

The three-dimensional (3D) organization of the human genome plays a critical role in regulating gene expression and is frequently disrupted in cancer. However, how key factors like Heterochromatin Protein 1 alpha (HP1) and Transforming Growth Factor beta (TGF{beta}) remodel this architecture to drive tumorigenesis remains poorly understood. We investigated the effects of HP1 knockdown and TGF{beta} treatment on higher-order chromatin structure and gene expression in human mammary epithelial cells. Our findings reveal that HP1 depletion and TGF{beta} stimulation exert distinct and opposing effects on genome compartmentalization and sub compartmentalization. HP1 knockdown drives a genome-wide shift of chromatin from transcriptionally inactive B compartments to active A compartments. This is accompanied by a stepwise redistribution of A subcompartments toward the most transcriptionally active state (A3), and the upregulation of oncogenic genes involved in EMT and proliferation. In contrast, TGF{beta} treatment promotes chromatin compaction, increases the proportion of B compartments, and drives a stepwise reduction in active A subcompartments. Our results highlight the differential roles of HP1 and TGF{beta} in shaping the 3D genome and underscore how precise, stepwise architectural changes contribute to malignant transformation. This study provides critical insight into how chromatin architecture acts as a regulatory layer in breast cancer development. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/705282v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@11c7475org.highwire.dtl.DTLVardef@121b305org.highwire.dtl.DTLVardef@1704b64org.highwire.dtl.DTLVardef@1659c34_HPS_FORMAT_FIGEXP M_FIG GRAPHICAL ABSTRACT C_FIG

genomics↗

bioRxiv2021

H2AFB1 is a cancer/testis gene involved in hyperactivation of ribosome biogenesis in Hodgkin Lymphoma

Testis-specific regulators of chromatin function are commonly ectopically expressed in human cancers, but their roles are poorly understood. Examination of 81 primary Hodgkin Lymphoma (HL) samples showed that the ectopic expression of the eutherian testis-specific histone variant H2A.B is an inherent feature of HL. In experiments using two HL-derived cell lines derived from different subtypes of HL, H2A.B knockdown inhibited cell proliferation. H2A.B was enriched in both the nucleoli of these HL cell lines and primary HL samples. We found that H2A.B enhanced ribosomal DNA (rDNA) transcription, was enriched at the rDNA promoter and transcribed regions, and interacted with RNA Pol I. Depletion of H2A.B caused the loss of RNA Pol I from rDNA chromatin. Remarkably, H2A.B was also required for high levels of ribosomal protein gene expression being located at the transcriptional start site and within the gene body. H2A.B knockdown reduced gene body chromatin accessibility of active RNA Pol II genes concurrent with a decrease in transcription. Taken together, our data show that in HL H2A.B has acquired a new function, the ability to increase ribosome biogenesis.

genomics↗

bioRxiv2017

Gene editing of the multi-copy H2A.B gene family by a single pair of TALENS

In view of the controversy related to the generation of off-target mutations by gene editing approaches, we tested the specificity of TALENs by disrupting a multi-copy gene family using only one pair of TALENS. We show here that TALENS do display a high level of specificity by simultaneously knocking out the function of the three genes that encode for H2A.B.3. This represents the first described knockout of this histone variant.

genomics↗