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Series GSE189303 Query DataSets for GSE189303
Status Public on Dec 16, 2021
Title Smad3 binding regions in human epidermal keratinocytes (HaCaT).
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Smad proteins transduce signals downstream of transforming growth factor-b (TGF-b), and are one of the factors that regulate the expression of genes related to diseases affecting the skin. In the present study, we identified MAB21L4, also known as male abnormal 21 like 4 or C2orf54, as one of the most up-regulated targets of TGF-b and Smad3 in differentiated human progenitor epidermal keratinocytes using chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq). Smad2 and Smad3 bound to the regulatory regions of the MAB21L4 gene locus. We found that TGF-b induced expression of the barrier protein involucrin (encoded by the IVL gene). Transcriptional activity of the IVL promoter induced by TGF-b was inhibited by siRNAs for MAB21L4. Further analysis revealed that MAB21L4 siRNAs also down-regulated the expression of several target genes of TGF-b. MAB21L4 protein was located mainly in the cytosol, where it was physically bound to Smad3 and a transcriptional corepressor c-Ski. siRNAs for MAB21L4 did not inhibit the binding of Smad3 to their target genomic regions but down-regulated acetylation of histone H3 lys 27 (H3K27ac), an active enhancer mark, near the Smad3 binding regions. These findings suggest that TGF-b-induced MAB21L4 up-regulates the gene expression induced by TGF-b, possibly through physical interactions with a transcriptional corepressor c-Ski in the cytosol.
Overall design Smad3 and Smad2 ChIP samples were sequenced for analysis.
Contributor(s) Ogami T, Tamura Y, Tsutsumi S, Aburatani H, Miyazawa K, Miyazono K, Koinuma D
Citation(s) 34908107
Submission date Nov 22, 2021
Last update date Dec 18, 2021
Contact name Daizo Koinuma
Organization name University of Tokyo
Department Pathology
Street address Hongo 7-3-1, Bunkyo-ku
City Tokyo
ZIP/Postal code 113-0033
Country Japan
Platforms (2)
GPL17301 Ion Torrent PGM (Homo sapiens)
GPL17303 Ion Torrent Proton (Homo sapiens)
Samples (5)
GSM5698659 Smad3 binding region in HaCaT cells stimulated with TGF-beta, replicate 1
GSM5698660 Smad3 binding region in HaCaT cells stimulated with TGF-beta, replicate 2
GSM5698661 control genomic data in HaCaT cells
This SubSeries is part of SuperSeries:
GSE180252 ChIP-seq and RNA-seq of Human progenitor epidermal keratinocytes (HPEK) and HaCaT cells
BioProject PRJNA782488

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Supplementary file Size Download File type/resource
GSE189303_RAW.tar 592.2 Mb (http)(custom) TAR (of BED, BEDGRAPH)
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Raw data are available in SRA
Processed data provided as supplementary file

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