Regulation of the microRNA processor DGCR8 by the tumor suppressor ING1

ABSTRACT: The ING familiy of tumor suppressor proteins control several cellular functions relevant to anti-tumor protection, like cell-cycle control, apoptosis, senescence or migration. ING proteins are functionally linked to the p53 pathway, and they participate in transcriptional control via the recognisition of histone marks and recruitment of protein complexes with chromatin-modifying activity to specific promoters. Here, we have investigated the global impact of ING1 in gene regulation through genome-wide analysis of expression profiles in primary embryonic fibroblasts deficient for the Ing1 locus. We find that Ing1 has a predominant role as transcriptional repressor in this setting, affecting the expression of genes involved in a variety of cellular functions. Within the subset of genes showing differential expression, we have identified DGCR8, a protein involved in the early steps of microRNA biogenesis. We show that ING1 binds to the DGCR8 promoter and controls its transcription through chromatin regulation at its promoter. We also find that ING1 and DGCR8 can cooperate in restraining proliferation. In summary, this study reveals a novel connection between ING1 and a regulator of microRNA biogenesis, and identifies new links between tumor suppressor proteins and the microRNA machinery For MEFs, two replicates were used for each genotype (wild-type or Ing1-deficient). Wild type MEFs were used as reference. For EMG cells [a cell line generated in our laboratory], two replicates were used for each condition (cells where ING1 was induced by doxycycline or uninduced cells). Uninduced cells were used as reference.

ORGANISM(S): Homo sapiens

SUBMITTER: Ignacio Palmero 

PROVIDER: E-GEOD-18645 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress