Your browser doesn't support javascript.
loading
Depletion of lamins B1 and B2 promotes chromatin mobility and induces differential gene expression by a mesoscale-motion-dependent mechanism.
Pujadas Liwag, Emily M; Wei, Xiaolong; Acosta, Nicolas; Carter, Lucas M; Yang, Jiekun; Almassalha, Luay M; Jain, Surbhi; Daneshkhah, Ali; Rao, Suhas S P; Seker-Polat, Fidan; MacQuarrie, Kyle L; Ibarra, Joe; Agrawal, Vasundhara; Aiden, Erez Lieberman; Kanemaki, Masato T; Backman, Vadim; Adli, Mazhar.
Afiliación
  • Pujadas Liwag EM; Department of Biomedical Engineering, Northwestern University, Evanston, IL, 60208, USA.
  • Wei X; IBIS Interdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, USA.
  • Acosta N; Center for Physical Genomics and Engineering, Northwestern University, Evanston, IL, 60208, USA.
  • Carter LM; Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA, 22903, USA.
  • Yang J; Department of Biomedical Engineering, Northwestern University, Evanston, IL, 60208, USA.
  • Almassalha LM; Center for Physical Genomics and Engineering, Northwestern University, Evanston, IL, 60208, USA.
  • Jain S; Department of Biomedical Engineering, Northwestern University, Evanston, IL, 60208, USA.
  • Daneshkhah A; IBIS Interdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, USA.
  • Rao SSP; Center for Physical Genomics and Engineering, Northwestern University, Evanston, IL, 60208, USA.
  • Seker-Polat F; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • MacQuarrie KL; Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
  • Ibarra J; Department of Biomedical Engineering, Northwestern University, Evanston, IL, 60208, USA.
  • Agrawal V; Center for Physical Genomics and Engineering, Northwestern University, Evanston, IL, 60208, USA.
  • Aiden EL; Department of Gastroenterology and Hepatology, Northwestern Memorial Hospital, Chicago, IL, 60611, USA.
  • Kanemaki MT; Department of Biomedical Engineering, Northwestern University, Evanston, IL, 60208, USA.
  • Backman V; Center for Physical Genomics and Engineering, Northwestern University, Evanston, IL, 60208, USA.
  • Adli M; Department of Biomedical Engineering, Northwestern University, Evanston, IL, 60208, USA.
Genome Biol ; 25(1): 77, 2024 03 22.
Article en En | MEDLINE | ID: mdl-38519987
ABSTRACT

BACKGROUND:

B-type lamins are critical nuclear envelope proteins that interact with the three-dimensional genomic architecture. However, identifying the direct roles of B-lamins on dynamic genome organization has been challenging as their joint depletion severely impacts cell viability. To overcome this, we engineered mammalian cells to rapidly and completely degrade endogenous B-type lamins using Auxin-inducible degron technology.

RESULTS:

Using live-cell Dual Partial Wave Spectroscopic (Dual-PWS) microscopy, Stochastic Optical Reconstruction Microscopy (STORM), in situ Hi-C, CRISPR-Sirius, and fluorescence in situ hybridization (FISH), we demonstrate that lamin B1 and lamin B2 are critical structural components of the nuclear periphery that create a repressive compartment for peripheral-associated genes. Lamin B1 and lamin B2 depletion minimally alters higher-order chromatin folding but disrupts cell morphology, significantly increases chromatin mobility, redistributes both constitutive and facultative heterochromatin, and induces differential gene expression both within and near lamin-associated domain (LAD) boundaries. Critically, we demonstrate that chromatin territories expand as upregulated genes within LADs radially shift inwards. Our results indicate that the mechanism of action of B-type lamins comes from their role in constraining chromatin motion and spatial positioning of gene-specific loci, heterochromatin, and chromatin domains.

CONCLUSIONS:

Our findings suggest that, while B-type lamin degradation does not significantly change genome topology, it has major implications for three-dimensional chromatin conformation at the single-cell level both at the lamina-associated periphery and the non-LAD-associated nuclear interior with concomitant genome-wide transcriptional changes. This raises intriguing questions about the individual and overlapping roles of lamin B1 and lamin B2 in cellular function and disease.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatina / Lamina Tipo B Límite: Animals Idioma: En Revista: Genome Biol Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatina / Lamina Tipo B Límite: Animals Idioma: En Revista: Genome Biol Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido