Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Comparative genomic hybridisation of gDNA from HDAC1-/-; HDAC2+/- diseased mouse thymocytes and sample matched wild-type tail

ABSTRACT: Histone deacetylase 1 and 2 (HDAC1/2) regulate chromatin structure as the catalytic core of the Sin3A, NuRD and CoREST co-repressor complexes. To better understand the key pathways regulated by HDAC1/2 in the adaptive immune system and inform their exploitation as drug targets, we have generated mice with a T cell specific deletion and performed comparative genomic hybridisation using genomic DNA from HDAC1-/-; HDAC2+/- diseased thymocytes and sample-matched, wild-type tail. A data set from a related transcription-profiling study comparing HDAC1-/-; HDAC2+/- mouse thymus tissue against thymus tissues from wild-type counterparts has also been deposited at ArrayExpress under accession E-MTAB-1432: http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1432

ORGANISM(S): Mus musculus

SUBMITTER: Oliver Dovey

PROVIDER: E-MTAB-1433 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Histone deacetylase 1 and 2 are essential for normal T-cell development and genomic stability in mice.

Dovey Oliver M OM Foster Charles T CT Conte Nathalie N Edwards Sally A SA Edwards Jennifer M JM Singh Rajinder R Vassiliou George G Bradley Allan A Cowley Shaun M SM

Blood 20130103 8

Histone deacetylase 1 and 2 (HDAC1/2) regulate chromatin structure as the catalytic core of the Sin3A, NuRD and CoREST co-repressor complexes. To better understand the key pathways regulated by HDAC1/2 in the adaptive immune system and inform their exploitation as drug targets, we have generated mice with a T-cell specific deletion. Loss of either HDAC1 or HDAC2 alone has little effect, while dual inactivation results in a 5-fold reduction in thymocyte cellularity, accompanied by developmental a ...[more]

PMID: 23287868

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Project description:Histone deacetylases (Hdac) remove acetyl groups from proteins, influencing global and specific gene expression. Hdacs control inflammation, as shown by Hdac inhibitor-dependent protection from DSS-induced murine colitis. While tissue-specific Hdac knockouts show redundant and specific functions, little is known of their intestinal epithelial cell (IEC) role. We have shown previously that dual Hdac1/Hdac2 IEC-specific loss disrupts cell proliferation and determination, with decreased secretory cell numbers and altered barrier function. We thus investigated how compound Hdac1/Hdac2 or Hdac2 IEC-specific deficiency alters the inflammatory response. Floxed Hdac1 and Hdac2 and villin-Cre mice were interbred. Compound Hdac1/Hdac2 IEC-deficient mice showed chronic basal inflammation, with increased basal Disease Activity Index (DAI) and deregulated Reg gene colonic expression. DSS-treated dual Hdac1/Hdac2 IEC-deficient mice displayed increased DAI, histological score, intestinal permeability and inflammatory gene expression. In contrast to double knockouts, Hdac2 IEC-specific loss did not affect IEC determination and growth, nor result in chronic inflammation. However, Hdac2 disruption protected against DSS colitis, as shown by decreased DAI, intestinal permeability and caspase-3 cleavage. Hdac2 IEC-specific deficient mice displayed increased expression of IEC gene subsets, such as colonic antimicrobial Reg3b and Reg3g mRNAs, and decreased expression of immune cell function-related genes. Our data show that Hdac1 and Hdac2 are essential IEC homeostasis regulators. IEC-specific Hdac1 and Hdac2 may act as epigenetic sensors and transmitters of environmental cues and regulate IEC-mediated mucosal homeostatic and inflammatory responses. Different levels of IEC Hdac activity may lead to positive or negative outcomes on intestinal homeostasis during inflammation Total RNAs from the colon of three control and three Hdac2 IEC-specific knockout mice were isolated with the Rneasy kit (Qiagen, Mississauga, ON, Canada).

Dataset Information

Comparative genomic hybridisation of gDNA from HDAC1-/-; HDAC2+/- diseased mouse thymocytes and sample matched wild-type tail

Publications

Histone deacetylase 1 and 2 are essential for normal T-cell development and genomic stability in mice.

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