Project description:Ten-eleven translocation (Tet) enzymes (Tet1/2/3) mediate 5-methylcytosine (5mC) hydroxylation, which can facilitate DNA demethylation and thereby impact gene expression. Studied mostly for how mutant isoforms impact cancer, the normal roles for Tet enzymes during organogenesis are largely unknown. By analyzing compound mutant zebrafish, we discovered a requirement for Tet2/3 activity in embryonic heart for recruitment of epicardial progenitors, associated with defects in development of the atrial-ventricular canal (AVC). Through a combination of methylation, hydroxymethylation, and transcript profiling, the genes encoding the ActivinA subunit Inhbaa (in endocardium) and Sox9b (in myocardium) were implicated as demethylation targets of Tet2/3 and critical for organization of AVC-localized extracellular matrix (ECM), facilitating migration of epicardial progenitors onto the developing heart tube. This study elucidates essential DNA epigenetic modifications that govern gene expression changes during cardiac development with striking temporal and lineage specificities, highlighting complex interactions in multiple cell populations during development of the vertebrate heart.

2019-01-15 | GSE121989 | GEO

Gene expression profiles of Tet1 knockout (T1KO), Tet2 knockout (T2KO) and Tet1/Tet2 double knockout (DKO) mouse embryonic stem cells.

Project description:Global gene expression profile of single and double mutant mouse ES cells were compared to wt ES cells. Two male Tet1 KO, one male Tet2 KO, two male double KO, two female double KO, two male WT and two female WT mouse ES cells were compared. Global gene expression profile of single and double knockout mouse embryonic stem cells were compared to that of wild type mouse ES cells. All used ES lines were derived from C57/BL/6 mixed background mice. RNA from feeder free mutant mouse ES cells was competetively hybridized against RNA from WT ES cells. Same sex lines were compared. Two independent ES line of each genotype were used, with the exception of Tet2 KO ES cells where only one male line was used.

2013-02-01 | E-GEOD-42991 | biostudies-arrayexpress

Gene expression profile of zebrafish synpo2 mutant

Project description:Embryonic zebrafish synpo2 mutants were compared to wild-type (22 hpf)

2021-01-01 | GSE150046 | GEO

Context Dependent Effects of Ascorbic Acid Treatment in TET2 Mutant Myeloid Neoplasia

Project description:Loss-of-function TET2 mutations (TET2MT) are common in myeloid neoplasia. TET2, a DNA dioxygenase, requires 2-oxoglutarate and Fe(II) to oxidize 5-methylcytosine. TET2MT thus result in hypermethylation and transcriptional repression. Ascorbic acid (AA) increases dioxygenase activity by facilitating Fe(III)/Fe(II) redox reaction and may alleviate some biological consequences of TET2MT by restoring dioxygenase activity. Here, we report the utility of AA in the prevention of TET2MT MN, clarify the mechanistic underpinning of the TET2-AA interactions, and demonstrate that the ability of AA to restore TET2 activity in cells depends on N- and C-terminal lysine acetylation and nature of TET2MT. Consequently, pharmacologic modulation of acetyltransferases and histone deacetylases may regulate TET dioxygenase-dependent AA effects. Thus, our study highlights the contribution of factors that may enhance or attenuate AA effects on TET2 and provides a rationale for novel therapeutic approaches including combinations of AA with class I/II HDAC inhibitor or sirtuin activators in TET2MT leukemia.

2020-09-09 | PXD020550 | Pride

RNA-seq of LSK isolated from U2af1 mutant, Tet2 mutant and U2af1/Tet2 double mutant against wild-type controls.

Project description:RNA-seq of LSK isolated from U2af1 mutant, Tet2 mutant and U2af1/Tet2 double mutant against wild-type controls.

| PRJEB44970 | ENA