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Identification of several potential chromatin binding sites of HOXB7 and its downstream target genes in breast cancer

ABSTRACT: We report the chromatin binding sites of HOXB7 transcription factor in BT-474 breast cancer cell line using ChIP-sequencing. We validated the chromatin binding sites in BT-474, MDA-MB-361, MCF7 and T-47D breast cancer cell lines using ChIP-qPCR. The ChIP experiments have been performed using HOXB7 antibody and IgG non-specific antibody as a negative control. The direct downstream target genes of HOXB7 were identified by analyzing the expression of genes located nearby HOXB7 binding sites in HOXB7 knockdown versus control cells using qRT-PCR.

ORGANISM(S): Homo sapiens

PROVIDER: GSE47164 | GEO | 2015/06/08

SECONDARY ACCESSION(S): PRJNA204940

REPOSITORIES: GEO

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Identification of several potential chromatin binding sites of HOXB7 and its downstream target genes in breast cancer

Project description:We report the chromatin binding sites of HOXB7 transcription factor in BT-474 breast cancer cell line using ChIP-sequencing. We validated the chromatin binding sites in BT-474, MDA-MB-361, MCF7 and T-47D breast cancer cell lines using ChIP-qPCR. The ChIP experiments have been performed using HOXB7 antibody and IgG non-specific antibody as a negative control. The direct downstream target genes of HOXB7 were identified by analyzing the expression of genes located nearby HOXB7 binding sites in HOXB7 knockdown versus control cells using qRT-PCR. Examination of chromatin binding sites of HOXB7 in BT-474 breast cancer cell line using ChIP-seq. Four parallel IgG samples were sequenced, merged together and used as a control data set. Two parallel HOXB7 ChIP samples were sequenced and merged for each replicate, AF1 and AF2. Both HOXB7 ChIP replicates (AF1 and AF2) contained approximately the same amount of reads as the merged IgG control data set.

2015-06-08 | E-GEOD-47164 | biostudies-arrayexpress

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HOXB7 is an ERÎ± cofactor in the activation of HER2 and multiple ER target genes leading to endocrine resistance

Project description:Why breast cancers become resistant to tamoxifen despite continued expression of the estrogen receptor alpha (ERÎ±) and what factors are responsible for high HER2 expression in these tumors remains an enigma. HOXB7 ChIP analysis followed by validation showed that HOXB7 physically interacts with ERÎ±, and that the HOXB7-ERÎ± complex enhances transcription of many ERÎ± target genes including HER2. Investigating strategies for controlling HOXB7, our studies revealed that MYC, stabilized via phosphorylation mediated by EGFR-HER2 signaling, inhibits transcription of miRNA-196a, a HOXB7 repressor. This leads to increased expression of HOXB7, ER-target genes and HER2. Repressing MYC using small molecule inhibitors reverses these events, and causes regression of breast cancer xenografts. The MYC-HOXB7-HER2 signaling pathway is eminently targetable in endocrine-resistant breast cancer. MCF7 cell lines stably transduced with either vector control of HOXB7. Array ran in duplicates.

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human HCC cell MHCCLM3: HOXB7-siRNA transfected vs. control

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