Histone methylation regulator PTIP orchestrates inflammatory responses via modulating acetylation state of cis-regulatory elements [ChIP-Seq]
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ABSTRACT:
PROVIDER: PRJNA686270 | ENA |
REPOSITORIES: ENA
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Project description:Innate immune cells including myeloid cells exhibit dynamic cellular switches during inflammatory and immune responses against infection. These processes are tightly regulated at different levels including the cis-regulatory elements of immune cells. However, it remains unclear how the dynamic states of cis-regulatory elements of innate immune cells are controlled during inflammatory responses. Here we found that histone methylation regulator PTIP orchestrates inflammatory responses of macrophages through regulating acetylation state of enhancers and promoters. Rapid elevated expression of PTIP is observed in primary human and mouse macrophages upon lipopolysaccharide (LPS) stimulation. Loss of PTIP represses transcription of pro-inflammatory genes, and activates expression of anti-inflammatory genes. Mechanistically, we found that, independent of its function in histone methylation, PTIP interacts with acetyltransferase p300 and deacetylase HDACs, and serves as a beacon to recruit them to specific sites of inflammatory genes respectively. PTIP deficiency alters H3K27 acetylation state of cis-regulatory elements of inflammatory genes. Moreover, PTIP and c-JUN shape a positive and feedforward regulatory circuit. In addition, PTIP deletion sustains immunosuppressive function of tumor-associated macrophages (TAMs) and promotes tumor growth. Overall, our findings uncover a critical role of PTIP in altering the acetylation state of cis-regulatory regions and fine-tuning the inflammatory responses of innate immune cells.
2022-12-30 | GSE163463 | GEO
Project description:Innate immune cells including myeloid cells exhibit dynamic cellular switches during inflammatory and immune responses against infection. These processes are tightly regulated at different levels including the cis-regulatory elements of immune cells. However, it remains unclear how the dynamic states of cis-regulatory elements of innate immune cells are controlled during inflammatory responses. Here we found that histone methylation regulator PTIP orchestrates inflammatory responses of macrophages through regulating acetylation state of enhancers and promoters. Rapid elevated expression of PTIP is observed in primary human and mouse macrophages upon lipopolysaccharide (LPS) stimulation. Loss of PTIP represses transcription of pro-inflammatory genes, and activates expression of anti-inflammatory genes. Mechanistically, we found that, independent of its function in histone methylation, PTIP interacts with acetyltransferase p300 and deacetylase HDACs, and serves as a beacon to recruit them to specific sites of inflammatory genes respectively. PTIP deficiency alters H3K27 acetylation state of cis-regulatory elements of inflammatory genes. Moreover, PTIP and c-JUN shape a positive and feedforward regulatory circuit. In addition, PTIP deletion sustains immunosuppressive function of tumor-associated macrophages (TAMs) and promotes tumor growth. Overall, our findings uncover a critical role of PTIP in altering the acetylation state of cis-regulatory regions and fine-tuning the inflammatory responses of innate immune cells.
2022-12-30 | GSE163208 | GEO
Project description:Innate immune cells including myeloid cells exhibit dynamic cellular switches during inflammatory and immune responses against infection. These processes are tightly regulated at different levels including the cis-regulatory elements of immune cells. However, it remains unclear how the dynamic states of cis-regulatory elements of innate immune cells are controlled during inflammatory responses. Here we found that histone methylation regulator PTIP orchestrates inflammatory responses of macrophages through regulating acetylation state of enhancers and promoters. Rapid elevated expression of PTIP is observed in primary human and mouse macrophages upon lipopolysaccharide (LPS) stimulation. Loss of PTIP represses transcription of pro-inflammatory genes, and activates expression of anti-inflammatory genes. Mechanistically, we found that, independent of its function in histone methylation, PTIP interacts with acetyltransferase p300 and deacetylase HDACs, and serves as a beacon to recruit them to specific sites of inflammatory genes respectively. PTIP deficiency alters H3K27 acetylation state of cis-regulatory elements of inflammatory genes. Moreover, PTIP and c-JUN shape a positive and feedforward regulatory circuit. In addition, PTIP deletion sustains immunosuppressive function of tumor-associated macrophages (TAMs) and promotes tumor growth. Overall, our findings uncover a critical role of PTIP in altering the acetylation state of cis-regulatory regions and fine-tuning the inflammatory responses of innate immune cells.
2022-12-30 | GSE163221 | GEO
Project description:Histone methylation regulator PTIP orchestrates inflammatory responses via modulating acetylation state of cis-regulatory elements
| PRJNA685639 | ENA
Project description:Histone methylation regulator PTIP orchestrates inflammatory responses via modulating acetylation state of cis-regulatory elements [BMDM-RNA-seq]
| PRJNA685197 | ENA
Project description:Histone methylation regulator PTIP orchestrates inflammatory responses via modulating acetylation state of cis-regulatory elements [TAM- RNA-seq]
| PRJNA685359 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-12-30 | GSE163293 | GEO
Project description:PPARg and C/EBPa cooperate to control preadipocyte differentiation (adipogenesis). However, the factors that regulate PPARg and C/EBPa expression during adipogenesis remain largely unclear. Here we show PTIP, a protein that associates with histone H3K4 methyltransferases, regulates PPARg and C/EBPa expression in mouse embryonic fibroblasts (MEFs) and during preadipocyte differentiation. PTIP deletion in MEFs leads to marked decreases of PPARg expression and PPARg-stimulated C/EBPα expression. Further, PTIP is essential for induction of PPARg and C/EBPa expression during preadipocyte differentiation. Deletion of PTIP impairs the enrichment of H3K4 trimethylation and RNA polymerase II on PPARg and C/EBPa promoters. Accordingly, PTIP-/- MEFs and preadipocytes all show striking defects in adipogenesis. Furthermore, rescue of the adipogenesis defect in PTIP-/- MEFs requires co-expression of PPARg and C/EBPa. Finally, deletion of PTIP in brown adipose tissue significantly reduces tissue weight in mice. Thus, by regulating PPARg and C/EBPa expression, PTIP plays a critical role in adipogenesis.
2009-05-29 | GSE16263 | GEO
Project description:PPARg and C/EBPa cooperate to control preadipocyte differentiation (adipogenesis). However, the factors that regulate PPARg and C/EBPa expression during adipogenesis remain largely unclear. Here we show PTIP, a protein that associates with histone H3K4 methyltransferases, regulates PPARg and C/EBPa expression in mouse embryonic fibroblasts (MEFs) and during preadipocyte differentiation. PTIP deletion in MEFs leads to marked decreases of PPARg expression and PPARg-stimulated C/EBPα expression. Further, PTIP is essential for induction of PPARg and C/EBPa expression during preadipocyte differentiation. Deletion of PTIP impairs the enrichment of H3K4 trimethylation and RNA polymerase II on PPARg and C/EBPa promoters. Accordingly, PTIP-/- MEFs and preadipocytes all show striking defects in adipogenesis. Furthermore, rescue of the adipogenesis defect in PTIP-/- MEFs requires co-expression of PPARg and C/EBPa. Finally, deletion of PTIP in brown adipose tissue significantly reduces tissue weight in mice. Thus, by regulating PPARg and C/EBPa expression, PTIP plays a critical role in adipogenesis. To identify PTIP-regulated genes, immortalized PTIP conditional knockout PTIPflox/flox MEFs were infected with retroviruses expressing either Cre recombinase or vector alone. We prepared duplicated RNAs from either vector or Cre infected cells (PTIP+/+ or PTIP-/-) for 4 affymetrix microarrays.
2009-05-29 | E-GEOD-16263 | biostudies-arrayexpress
Project description:Programmed genetic rearrangements in lymphocytes require transcription at antigen receptor genes to promote accessibility for initiating double-strand break (DSB) formation critical for DNA recombination and repair. Here we show that activated B cells deficient in the PTIP component of the MLL3 (mixed-lineage leukemia 3) /MLL4 complex display impaired histone methylation (H3K4me3) and transcription initiation of downstream switch regions at the immunoglobulin heavy-chain (Igh) locus leading to defective immunoglobulin class-switching. We also show that PTIP accumulation at DSBs contributes to class-switch recombination (CSR) and genome stability independently from Igh switch transcription. These results demonstrate that PTIP promotes specific chromatin changes that control the accessibility of the Igh locus to CSR, and suggest a non-redundant role for the MLL3/MLL4 complex in altering antibody effector function. Genome-wide analysis of histone modifications, PTIP, and Pol II in PTIP-WT and PTIP-KO mouse activated B cells.
2010-08-25 | E-GEOD-20852 | biostudies-arrayexpress