Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE140611 | GEO | 2020/04/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Dichotomous engagement of HDAC3 activity governs inflammatory responses.

Project description:The histone deacetylases (HDACs) are a superfamily of chromatin-modifying enzymes that silence transcription through the modification of histones. Among them, HDAC3 is unique in that interaction with nuclear receptor corepressors 1 and 2 (NCoR1/2) is required to engage its catalytic activity1-3. However, global loss of HDAC3 also results in the repression of transcription, the mechanism of which is currently unclear4-8. Here we report that, during the activation of macrophages by lipopolysaccharides, HDAC3 is recruited to activating transcription factor 2 (ATF2)-bound sites without NCoR1/2 and activates the expression of inflammatory genes through a non-canonical mechanism. By contrast, the deacetylase activity of HDAC3 is selectively engaged at ATF3-bound sites that suppress Toll-like receptor signalling. Loss of HDAC3 in macrophages safeguards mice from lethal exposure to lipopolysaccharides, but this protection is not conferred upon genetic or pharmacological abolition of the catalytic activity of HDAC3. Our findings show that HDAC3 is a dichotomous transcriptional activator and repressor, with a non-canonical deacetylase-independent function that is vital for the innate immune system.

| S-EPMC7725280 | biostudies-literature

Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses [ChIP-Seq]

Project description:Histone deacetylase 3 (HDAC3) is unique among the HDAC superfamily of chromatin modifiers that silence transcription through enzymatic modification of histones, because interaction with nuclear receptor corepressors (NCoR1/2) is required for engagement of its catalytic activity. However, loss of HDAC3 also represses transcription. Here we report that, during lipopolysaccharide (LPS) activation of macrophages, the deacetylase activity of HDAC3 is selectively engaged at ATF3-bound enhancers that repress anti-inflammatory genes. By contrast, LPS-stimulated recruitment of HDAC3 to ATF2-bound sites without NCoR1/2 activates pro-inflammatory genes by a non-canonical mechanism whereby catalytically inactive HDAC3 stably interacts with p65. Consistent with this bimodal inflammatory modulation, deletion of HDAC3 in macrophages safeguards mice from lethal exposure to LPS, but this protection is not conferred by genetic or pharmacological abolition of HDAC3 catalytic activity. Thus, HDAC3 is a dichotomous transcriptional activator and repressor whose deacetylase-independent functions are critical in priming the innate immune system.

2020-04-30 | GSE140581 | GEO

Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses [GRO-Seq]

2020-04-30 | GSE140573 | GEO

Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses [RNA-Seq]

2020-04-30 | GSE140610 | GEO

Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses

Project description:Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses

| PRJNA590241 | ENA

Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses [GRO-Seq]

Project description:Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses [GRO-Seq]

| PRJNA590194 | ENA

Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses [ChIP-Seq]