Idioma:

DACH1 protects podocytes from experimental diabetic injury and modulates PTIP-H3K4Me3 activity

Cao, Aili ; Li, Jianhua ; Asadi, Morad ; Basgen, John M ; Zhu, Bingbing ; Yi, Zhengzi ; Jiang, Song ; Doke, Tomohito ; El Shamy, Osama ; Patel, Niralee ; Cravedi, Paolo ; Azeloglu, Evren U ; Campbell, Kirk N ; Menon, Madhav ; Coca, Steve ; Zhang, Weijia ; Wang, Hao ; Zen, Ke ; Liu, Zhihong ; Murphy, Barbara ; He, John C ; D'Agati, Vivette D ; Susztak, Katalin ; Kaufman, Lewis

The Journal of clinical investigation, 2021-05, Vol.131 (10), p.1-17 [Periódico revisado por pares]

United States: American Society for Clinical Investigation

Texto completo disponível

Citações Citado por

Enviar para

Título:
DACH1 protects podocytes from experimental diabetic injury and modulates PTIP-H3K4Me3 activity
Autor: Cao, Aili ; Li, Jianhua ; Asadi, Morad ; Basgen, John M ; Zhu, Bingbing ; Yi, Zhengzi ; Jiang, Song ; Doke, Tomohito ; El Shamy, Osama ; Patel, Niralee ; Cravedi, Paolo ; Azeloglu, Evren U ; Campbell, Kirk N ; Menon, Madhav ; Coca, Steve ; Zhang, Weijia ; Wang, Hao ; Zen, Ke ; Liu, Zhihong ; Murphy, Barbara ; He, John C ; D'Agati, Vivette D ; Susztak, Katalin ; Kaufman, Lewis
Assuntos: Analysis ; Binding sites ; Biomedical research ; Biotechnology industry ; Clinical outcomes ; Derepression ; Development and progression ; Diabetes ; Diabetes mellitus ; Disease susceptibility ; DNA sequencing ; Epigenetic inheritance ; Epigenetics ; Epithelial cells ; Gene expression ; Genes ; Genetic aspects ; Genetic transcription ; Health aspects ; Histone H3 ; Histones ; HIV ; Human immunodeficiency virus ; Hyperglycemia ; Hypoplasia ; Kidney diseases ; Kidney glomerulus ; Lysine ; Mice ; Mutation ; Nucleotide sequence ; Nucleotide sequencing ; Pathogenesis ; Physiological aspects ; Proteins ; RNA ; RNA sequencing ; Rodents ; Transcription ; Transcription factors ; Transcriptomics
É parte de: The Journal of clinical investigation, 2021-05, Vol.131 (10), p.1-17
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: Dachshund homolog 1 (DACH1), a key cell-fate determinant, regulates transcription by DNA sequence-specific binding. We identified diminished Dach1 expression in a large-scale screen for mutations that convert injury-resistant podocytes into injury-susceptible podocytes. In diabetic kidney disease (DKD) patients, podocyte DACH1 expression levels are diminished, a condition that strongly correlates with poor clinical outcomes. Global Dach1 KO mice manifest renal hypoplasia and die perinatally. Podocyte-specific Dach1 KO mice, however, maintain normal glomerular architecture at baseline, but rapidly exhibit podocyte injury after diabetes onset. Furthermore, podocyte-specific augmentation of DACH1 expression in mice protects from DKD. Combined RNA sequencing and in silico promoter analysis reveal conversely overlapping glomerular transcriptomic signatures between podocyte-specific Dach1 and Pax transactivation-domain interacting protein (Ptip) KO mice, with upregulated genes possessing higher-than-expected numbers of promoter Dach1-binding sites. PTIP, an essential component of the activating histone H3 lysine 4 trimethylation (H3K4Me3) complex, interacts with DACH1 and is recruited by DACH1 to its promoter-binding sites. DACH1-PTIP recruitment represses transcription and reduces promoter H3K4Me3 levels. DACH1 knockdown in podocytes combined with hyperglycemia triggers target gene upregulation and increases promoter H3K4Me3. These findings reveal that in DKD, diminished DACH1 expression enhances podocyte injury vulnerability via epigenetic derepression of its target genes.
Editor: United States: American Society for Clinical Investigation
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Anterior Resultado 3 Avançar Ir para próxima página

Realização: Logos de Redes Sociais:

DACH1 protects podocytes from experimental diabetic injury and modulates PTIP-H3K4Me3 activity

United States: American Society for Clinical Investigation

Buscando em bases de dados remotas. Favor aguardar.