Elucidating altered transcriptional programs
Phone: 617.643.2579; Fax: 617.643.3170; E-mail: Bardeesy. Phone: 617.643.3156; Fax: 617.643.3170; E-mail: Tzatsos. (A) Heat map of quantitative RT-PCR data showing relative expression of HDM family members in human PDAC cell lines versus HPDE cells. (B) KDM2B transcript levels in a series of human PDAC specimens compared with normal pancreatic tissue, determined by RNA-seq (samples from MGH tumor bank).
First, PLZF bound and regulated genes encoding cytokine receptors as well as homing and adhesion receptors; second, PLZF bound and activated T-helper–specific transcription factor genes that in turn control T-helper–specific programs; finally, PLZF bound and suppressed the transcription of , a potent general repressor of effector differentiation in naive T cells.
These findings reveal the multilayered architecture of the transcriptional program recruited by PLZF and elucidate how a single transcription factor can drive the developmental acquisition of a broad effector program.
The most frequent genetic abnormality in T-ALL is the dysregulation of transcription factor genes.
We previously identified the “core transcriptional regulatory circuits” controlled by the oncogenic transcription factor TAL1 in T-ALL.
Together, these studies define expanded roles for SMYD3 and PC4 in gene regulation and provide an unprecedented documentation of their cooperative functions in stimulating oncogenic transcription.
SET and MYND domain-containing proteins (SMYD) are a special class of protein lysine methyltransferases involved in methylation of histones and non-histone proteins (1–3).Whereas C57BL/6 mice produce predominantly NKT cells with a T-bet–dependent type 1 helper phenotype (NKT1), other strains, including BALB/c, also express substantial populations of so-called NKT2 and NKT17 cells with polarized type 2 and type 17 helper programs controlled by GATA3 and RORγt, respectively.The BTB-zinc finger transcription factor PLZF (promyelocytic leukemia zinc finger, encoded by ), is specifically expressed in NKT cells, but not in conventional T cells or NK cells, and directs the acquisition of several key components of the NKT cell effector program during development, including cytokine and migration properties (4 abrogate both the expansion and the effector-memory differentiation of NKT cells, resulting in reversal to a naive phenotype and redistribution to the lymph nodes and circulating blood. Authorship note: Polina Paskaleva and Francesco Ferrari contributed equally to this work. in: JCI | Pub Med | Google Scholar Constellation Pharmaceuticals, Cambridge, Massachusetts, USA. Phone: 617.643.2579; Fax: 617.643.3170; E-mail: Bardeesy. Phone: 617.643.3156; Fax: 617.643.3170; E-mail: Tzatsos. KDM2B bound transcriptional start sites (TSSs) in discrete modules with these transcriptional regulators, leading to either stable repression or activation of gene expression. Address correspondence to: Alexandros Tzatsos or Nabeel Bardeesy, 185 Cambridge Street, Boston, Massachusetts 02114, USA. Functional interactions with Polycomb group (Pc G) complexes overrode cell fate decisions, whereas with interplay, MYC and KDM5A sustained metabolic gene expression.Notably, PLZF also bound and repressed )] is induced during the development of innate and innate-like lymphocytes to direct their acquisition of a T-helper effector program, but the molecular mechanisms involved are poorly understood.