A clinicopathological study of B-cell differentiation markers and transcription factors in classical Hodgkin's lymphoma: a potential prognostic role of MUM1/IRF4

The interferon-inducible DNA sensor IFI16 is involved in the modulation of cellular survival, proliferation, and differentiation. In the hematopoietic system, IFI16 is consistently expressed in the CD34+ stem cells and in peripheral blood lymphocytes; however, little is known regarding its regulation during maturation of B- and T-cells. We explored the role of IFI16 in normal B-cell subsets by analysing its expression and relationship with the major transcription factors involved in germinal center (GC) development and plasma-cell (PC) maturation.IFI16mRNA was differentially expressed in B-cell subsets with significant decrease inIFI16mRNA in GC and PCs with respect to naïve and memory subsets.IFI16mRNA expression is inversely correlated with a few master regulators of B-cell differentiation such asBCL6, XBP1, POU2AF1, andBLIMP1. In contrast,IFI16expression positively correlated withSTAT3, REL, SPIB, RELA, RELB, IRF4, STAT5B, andSTAT5A. ARACNE algorithm indicated a direct regulation ofIFI16byBCL6,STAT5B, andRELB, whereas the relationship betweenIFI16and the other factors is modulated by intermediate factors. In addition, analysis of the CD40 signaling pathway showed thatIFI16gene expression directly correlated with NF-κB activation, indicating that IFI16 could be considered an upstream modulator of NF-κB in human B-cells.

Download Full-text

Chromatin reader Dido3 regulates the genetic network of B cell differentiation

10.1101/2021.02.23.432411 ◽

2021 ◽

Author(s):

Fernando Gutiérrez del Burgo ◽

Tirso Pons ◽

Enrique Vázquez de Luis ◽

Carlos Martínez-A ◽

Ricardo Villares

Keyword(s):

Transcription Factors ◽

Cell Differentiation ◽

B Cell ◽

Cell Lineage ◽

Genetic Network ◽

B Cell Differentiation ◽

Differentiation Markers ◽

Hematopoietic Stem ◽

Severe Deficiency ◽

The Impact

ABSTRACTThe development of hematopoietic lineages is based on a complex balance of transcription factors whose expression depends on the epigenetic signatures that characterize each differentiation step. The B cell lineage arises from hematopoietic stem cells through the stepwise silencing of stemness genes and balanced expression of mutually regulated transcription factors, as well as DNA rearrangement. Here we report the impact on B cell differentiation of the lack of DIDO3, a reader of chromatin status, in the mouse hematopoietic compartment. We found reduced DNA accessibility in hematopoietic precursors, leading to severe deficiency in the generation of successive B cell differentiation stages. The expression of essential transcription factors and differentiation markers is affected, as is the somatic recombination process.One Sentence Summary: Epigenetic control of early hematopoiesis

Download Full-text

ETS1 encoding a transcription factor involved in B-cell differentiation is recurrently deleted and down-regulated in classical Hodgkin's lymphoma

Haematologica ◽

10.3324/haematol.2012.061770 ◽

2012 ◽

Vol 97 (10) ◽

pp. 1612-1614 ◽

Cited By ~ 9

Author(s):

B. M. Overbeck ◽

J. I. Martin-Subero ◽

O. Ammerpohl ◽

W. Klapper ◽

R. Siebert ◽

...

Keyword(s):

Transcription Factor ◽

Cell Differentiation ◽

B Cell ◽

Hodgkin’S Lymphoma ◽

Hodgkin's Lymphoma ◽

B Cell Differentiation

Download Full-text

Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription

Journal of Experimental Medicine ◽

10.1084/jem.20160514 ◽

2017 ◽

Vol 214 (7) ◽

pp. 2059-2071 ◽

Cited By ~ 11

Author(s):

Kenia Ubieta ◽

Mireia Garcia ◽

Bettina Grötsch ◽

Steffen Uebe ◽

Georg F. Weber ◽

...

Keyword(s):

Cell Proliferation ◽

Transcription Factors ◽

Cell Differentiation ◽

B Cells ◽

B Cell ◽

Cell Development ◽

B Cell Development ◽

Gene Profiling ◽

B Cell Differentiation

The role of AP-1 transcription factors in early B cell development and function is still incompletely characterized. Here we address the role of Fra-2 in B cell differentiation. Deletion of Fra-2 leads to impaired B cell proliferation in the bone marrow. In addition, IL-7–stimulated pro–B cell cultures revealed a reduced differentiation from large pre–B cells to small B cells and immature B cells. Gene profiling and chromatin immunoprecipitation sequencing analyses unraveled a transcriptional reduction of the transcription factors Foxo1, Irf4, Ikaros, and Aiolos in Fra-2–deficient B cells. Moreover, expression of IL7Rα and Rag 1/2, downstream targets of Irf4 and Foxo1, were also reduced in the absence of Fra-2. Pro–B cell proliferation and small pre–B cell differentiation were fully rescued by expression of Foxo1 and Irf4 in Fra-2–deficient pro–B cells. Hence, Fra-2 is a key upstream regulator of Foxo1 and Irf4 expression and influences proliferation and differentiation of B cells at multiple stages.

Download Full-text

New type of t(14; 18) in a non-Hodgkin's lymphoma provides insight in molecular events in early B-cell differentiation

British Journal of Haematology ◽

10.1111/j.1365-2141.1995.tb05359.x ◽

1995 ◽

Vol 91 (3) ◽

pp. 630-639 ◽

Cited By ~ 16

Author(s):

J. P. P. Meijerink ◽

J. M. M. Raemaekers ◽

E. J. B. M. Mensink

Keyword(s):

Cell Differentiation ◽

B Cell ◽

Hodgkin’S Lymphoma ◽

Hodgkin's Lymphoma ◽

B Cell Differentiation ◽

Non Hodgkin’S Lymphoma ◽

Molecular Events ◽

Non Hodgkin's Lymphoma ◽

New Type

Download Full-text

Chromatin Reader Dido3 Regulates the Genetic Network of B Cell Differentiation

10.21203/rs.3.rs-1031396/v1 ◽

2021 ◽

Author(s):

Fernando Gutiérrez del Burgo ◽

Tirso Pons ◽

Enrique Vázquez de Luis ◽

Carlos Martínez-A ◽

Ricardo Villares

Keyword(s):

Transcription Factors ◽

Cell Differentiation ◽

B Cell ◽

Specific Activity ◽

Cell Lineage ◽

Genetic Network ◽

B Cell Differentiation ◽

Differentiation Markers ◽

Hematopoietic Stem ◽

The Impact

Abstract BACKGROUNDThe development of hematopoietic lineages is based on a complex balance of transcription factors whose expression depends on the epigenetic signatures that characterize each differentiation step. The B cell lineage arises from hematopoietic stem cells through the stepwise silencing of stemness genes and balanced expression of mutually regulated transcription factors, as well as DNA rearrangement, in a complex process involving epigenetic remodeling.RESULTSHere we report the impact on B cell differentiation of the lack of DIDO3, a reader of histone post-translational modifications, in the mouse hematopoietic compartment. We found reduced DNA accessibility in hematopoietic precursors, leading to a severe deficiency specifically in the generation of successive stages of B-cell differentiation. The expression of essential transcription factors and differentiation markers is impaired, as is the process of somatic recombination. DIDO3-deficient cells show transcriptional alterations of a number of polycomb repressive complex 2, suggesting the involvement of DIDO3 in determining the specific activity of PRC2 in the B cell lineage, including VH-DJH rearrangement. CONCLUSIONSTaken together, our data suggest that DIDO3 is an epigenetic reader involved in the specific differentiation of B cell precursors in the hematopoietic compartment of mice.

Download Full-text