Project description:White adipose tissue (WAT) plays a central role in lipid storage and systemic energy, lipid, and glucose homeostasis. Understanding the intricacies of adipocyte formation could inform therapies for obesity and metabolic disorders. We have identified the POZ/BTB and AT Hook Containing Zinc Finger 1 (PATZ1) protein as an adipogenic transcription factor through an unbiased high-throughput cDNA screen for transcriptional modulators of adipogenesis. PATZ1 is expressed by both human and mouse adipocyte precursor cells (APCs) and adipocytes, and in cell models, PATZ1 expression promotes adipogenesis through a mechanism dependent on protein-protein interaction and DNA binding. Both adipocyte-specific and APC-specific ablation of PATZ1 in mice leads to decreased fat mass and hypertrophied adipocytes. Genome-wide PATZ1 DNA binding analyses using ChIP-Seq suggest PATZ1 facilitates adipogenesis through interactions with transcription factor machinery at the promoter regions of critical early adipogenic factors and histone modifiers. Purification of the PATZ1 complex showed that General Transcription Factor 2I (GTF2I) associates with PATZ1 in a differentiation-dependent manner. Downregulation of GTF2I levels during adipogenesis markedly augments PATZ1 adipogenic function, suggesting a repressive interaction between GTF2I and PATZ1. These findings identify PATZ1 as a regulator of both adiposity and adipocyte differentiation programs and advance our understanding of the complex transcriptional mechanisms underlying adipose tissue development and homeostasis.
Project description:White adipose tissue (WAT) plays a central role in lipid storage and systemic energy, lipid, and glucose homeostasis. Understanding the intricacies of adipocyte formation could inform therapies for obesity and metabolic disorders. We have identified the POZ/BTB and AT Hook Containing Zinc Finger 1 (PATZ1) protein as an adipogenic transcription factor through an unbiased high-throughput cDNA screen for transcriptional modulators of adipogenesis. PATZ1 is expressed by both human and mouse adipocyte precursor cells (APCs) and adipocytes, and in cell models, PATZ1 expression promotes adipogenesis through a mechanism dependent on protein-protein interaction and DNA binding. Both adipocyte-specific and APC-specific ablation of PATZ1 in mice leads to decreased fat mass and hypertrophied adipocytes. Genome-wide PATZ1 DNA binding analyses using ChIP-Seq suggest PATZ1 facilitates adipogenesis through interactions with transcription factor machinery at the promoter regions of critical early adipogenic factors and histone modifiers. Purification of the PATZ1 complex showed that General Transcription Factor 2I (GTF2I) associates with PATZ1 in a differentiation-dependent manner. Downregulation of GTF2I levels during adipogenesis markedly augments PATZ1 adipogenic function, suggesting a repressive interaction between GTF2I and PATZ1. These findings identify PATZ1 as a regulator of both adiposity and adipocyte differentiation programs and advance our understanding of the complex transcriptional mechanisms underlying adipose tissue development and homeostasis.
Project description:White adipose tissue (WAT) plays a central role in lipid storage and systemic energy, lipid, and glucose homeostasis. Understanding the intricacies of adipocyte formation could inform therapies for obesity and metabolic disorders. We have identified the POZ/BTB and AT Hook Containing Zinc Finger 1 (PATZ1) protein as an adipogenic transcription factor through an unbiased high-throughput cDNA screen for transcriptional modulators of adipogenesis. PATZ1 is expressed by both human and mouse adipocyte precursor cells (APCs) and adipocytes, and in cell models, PATZ1 expression promotes adipogenesis through a mechanism dependent on protein-protein interaction and DNA binding. Both adipocyte-specific and APC-specific ablation of PATZ1 in mice leads to decreased fat mass and hypertrophied adipocytes. Genome-wide PATZ1 DNA binding analyses using ChIP-Seq suggest PATZ1 facilitates adipogenesis through interactions with transcription factor machinery at the promoter regions of critical early adipogenic factors and histone modifiers. Purification of the PATZ1 complex showed that General Transcription Factor 2I (GTF2I) associates with PATZ1 in a differentiation-dependent manner. Downregulation of GTF2I levels during adipogenesis markedly augments PATZ1 adipogenic function, suggesting a repressive interaction between GTF2I and PATZ1. These findings identify PATZ1 as a regulator of both adiposity and adipocyte differentiation programs and advance our understanding of the complex transcriptional mechanisms underlying adipose tissue development and homeostasis.
Project description:White adipose tissue (WAT) plays a central role in lipid storage and systemic energy, lipid, and glucose homeostasis. Understanding the intricacies of adipocyte formation could inform therapies for obesity and metabolic disorders. We have identified the POZ/BTB and AT Hook Containing Zinc Finger 1 (PATZ1) protein as an adipogenic transcription factor through an unbiased high-throughput cDNA screen for transcriptional modulators of adipogenesis. PATZ1 is expressed by both human and mouse adipocyte precursor cells (APCs) and adipocytes, and in cell models, PATZ1 expression promotes adipogenesis through a mechanism dependent on protein-protein interaction and DNA binding. Both adipocyte-specific and APC-specific ablation of PATZ1 in mice leads to decreased fat mass and hypertrophied adipocytes. Genome-wide PATZ1 DNA binding analyses using ChIP-Seq suggest PATZ1 facilitates adipogenesis through interactions with transcription factor machinery at the promoter regions of critical early adipogenic factors and histone modifiers. Purification of the PATZ1 complex showed that General Transcription Factor 2I (GTF2I) associates with PATZ1 in a differentiation-dependent manner. Downregulation of GTF2I levels during adipogenesis markedly augments PATZ1 adipogenic function, suggesting a repressive interaction between GTF2I and PATZ1. These findings identify PATZ1 as a regulator of both adiposity and adipocyte differentiation programs and advance our understanding of the complex transcriptional mechanisms underlying adipose tissue development and homeostasis.
Project description:Transcription factor PATZ1 promotes adipogenesis by controlling promoter regulatory loci of adipogenic factors [ChIPreChIPseq_D0_D5]
Project description:Transcription factor PATZ1 promotes adipogenesis by controlling promoter regulatory loci of adipogenic factors [ChIPseq_D-2_D0_D5_D8]
Project description:White adipose tissue (WAT) is essential for lipid storage and systemic energy homeostasis. Understanding adipocyte formation and stability is key to developing therapies for obesity and metabolic disorders. Through a high-throughput cDNA screen, we identified PATZ1, a POZ/BTB and AT-Hook Containing Zinc Finger 1 protein, as an important adipogenic transcription factor. PATZ1 is expressed in human and mouse adipocyte precursor cells (APCs) and adipocytes. In cellular models, PATZ1 promotes adipogenesis via protein-protein interactions and DNA binding. PATZ1 ablation in mouse adipocytes and APCs leads to a reduced APC pool, decreased fat mass, and hypertrophied adipocytes. ChIP-Seq and RNA-seq analyses show that PATZ1 supports adipogenesis by interacting with transcriptional machinery at the promoter regions of key early adipogenic factors. Mass-spec results show that PATZ1 associates with GTF2I, with GTF2I modulating PATZ1's function during differentiation. These findings underscore PATZ1's regulatory role in adipocyte differentiation and adiposity, offering insights into adipose tissue development.
Project description:Bone marrow stromal cells (BMSCs) were isolated from the femora and tibiae of irtTA-GBD*-TAg transgenic mice. Using cellular cloning we established skeletal progenitors with unipotent osteogenic and adipogenic properties. Previous RNA-seq analysis of more progenitor types revealed differential expression in members of the Interferon-gamma (IFNγ) signaling pathway. Treatment of adipogenic progenitors with IFNγ inhibited adipogenesis and promoted osteogenesis. RNA-seq analysis of osteogenic, adipogenic and IFNγ treated adipogenic clones revealed factors controlling the osteogenic versus adipogenic commitment of bone marrow skeletal progenitors.
Project description:Insults to cellular health cause p53 protein accumulation and loss of p53 function leads to tumorigenesis. Thus, p53 has to be tightly controlled. Here we report that the BTB/POZ domain transcription factor PATZ1 (MAZR), previously known for its transcriptional suppressor functions in T lymphocytes, is a crucial regulator of p53. The novel inhibitory role of PATZ1 on the p53 protein marks it as a proto-oncogene. PATZ1 deficient cells have reduced proliferative capacity which we assess by RNASeq and real time cell growth rate analysis. PATZ1 modifies the expression of p53 target genes associated with cell proliferation gene ontology terms. Moreover, PATZ1 regulates several genes involved in cellular adhesion and morphogenesis. Significantly, treatment with the DNA damage inducing drug doxorubicin results in the loss of the PATZ1 transcription factor, as p53 accumulates. We find that PATZ1 binds to p53 and inhibits p53 dependent transcription activation. We examine the mechanism of this functional inhibitory interaction and demonstrate that PATZ1 excludes p53 from DNA binding. This study documents PATZ1 as a novel player in the p53 pathway. RNA-seq was used to define differentially expressed genes in wild-type and PATZ1-/- MEFs. Each sample was represented in triplicate.