EP300-HDAC1-SWI/SNF functional unit defines transcription of some DNA repair enzymes during differentiation of human macrophages

Publication date: Available online 8 November 2018Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory MechanismsAuthor(s): Julita Pietrzak, Tomasz Płoszaj, Łukasz Pułaski, Agnieszka RobaszkiewiczAbstractDifferentiation of human macrophages predisposes these cells to numerous tasks, i.e. killing invading pathogens, and this entails the need for enhanced intracellular defences against stress, including conditions that may increase DNA damage. Our study shows that expression of DNA repair enzymes, such as PARP1, BRCA1 and XRCC1, are activated during macrophage development by the SWI/SNF chromatin remodelling complex, which serves as a histone acetylation sensor. It recognises and displaces epigenetically marked nucleosomes, thereby enabling transcription. Acetylation is controlled both in monocytes and macrophages by the co-operation of EP300 and HDAC1 activities. Differentiation modulates the activities of individual components of EP300-HDAC1-SWI/SNF functional unit and entails recruitment of PBAF to gene promoters. In monocytes, histone-deacetylated promoters of repressed PARP1, BRCA1 and XRCC1 respond only to HDAC inhibition, with an opening of the chromatin structure by BRM, whereas in macrophages both EP300 and HDAC1 contribute to the fine-tuning of nucleosomal acetylation, with HDAC1 remaining active and the balance of EP300 and HDAC1 activities controlling nucleosome eviction by BRG1-containing SWI/SNF. Since EP300-HDAC1-SWI/SNF operates at the level of gene ...
Source: Biochimica et Biophysica Acta (BBA) Gene Regulatory Mechanisms - Category: Genetics & Stem Cells Source Type: research