Emeritus Laboratory Rudolf Grosschedl
Cellular and Molecular Immunology
Differentiation of hematopoietic stem cells to specialized effector cells involves multiple cell fate choices and a progressive loss of lineage potential. We study how transcription factors change the epigenetic landscape, activate cell type-specific gene expression and ensure the maintenance of lineage identity. We use B lymphopoiesis as a model system and investigate how progenitor cells commit to the B cell lineage. We found that EBF1 acts as a pioneer transcription factor that regulates the transition of naive progenitor chromatin to B-lineage-committed chromatin. In addition, we examine the role of Satb transcription factors in the regulation of higher-order chromatin and differentiation of B cells and embryonic stem cells.
Approach
We use gene editing, genome-wide molecular and cell biological approaches in combination with primary cell transduction and mouse transgenic analysis to gain insight into the regulatory networks of B cell differentiation.
Impact
Our research is aimed at understanding how the correct dosage and function of transcription factors safeguard B lymphoid cells against leukemic transformation.
Selected Publications
1.
Phongbunchoo Y, Braikia FZ, Pessoa-Rodrigues C, Ramamoorthy S, Ramachandran H, Grosschedl A, Ma F, Cauchy P, Akhtar A, Sen R, Mittler G, Grosschedl R (2024)
YY1-mediated enhancer-promoter communication in the immunoglobulin μ locus is regulated by MSL/MOF recruitment.
Cell Report 43(7), 114456.
2.
Zolotarev N, Wang Y, Du M, Bayer M, Grosschedl A, Cisse I, Grosschedl R (2024)
Regularly spaced tyrosines in EBF1 mediate BRG1 recruitment and formation of nuclear subdiffractive clusters.
Genes Development 38(1-2), 4-10.
3.
Wang Y, Zolotarev N, Yang CY, Rambold A., Mittler G, Grosschedl R (2020)
A Prion-like Domain in Transcription Factor EBF1 Promotes Phase Separation and Enables B Cell Programming of Progenitor Chromatin
Immunity 53(6), 1151-1167.e6
4.
Derecka M, Herman JS, Cauchy P, Ramamoorthy S, Lupar E, Grün D, Grosschedl R (2020)
EBF1-deficient bone marrow stroma elicits persistent changes in HSC potential
Nature Immunology 21, 261-273.
5.
Li R, Cauchy P, Ramamoorthy S, Boller S, Chavez L, Grosschedl R (2018)
Dynamic EBF1 occupancy directs sequential epigenetic and transcriptional events in B-cell programming.
Genes Development 32, 96-111.
6.
Nechanitzky R, Akbas D, Scherer S, Györy I, Hoyler T, Ramamoorthy S, Diefenbach A, and Grosschedl R (2013)
Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells
Nature Immunology 14(8), 867-875.
More publications
