Elucidation of the Fanconi Anemia Protein Network in Meoisis and Its Function in the Regulation of Histone Modifications

作者：Alavattam Kris G; Kato Yasuko; Sin Ho Su; Maezawa So; Kowalski Ian J; Zhang Fan; Pang Qishen; Andreassen Paul R; Namekawa Satoshi H

来源：Cell Reports, 2016, 17(4): 1141-1157.

DOI：10.1016/j.celrep.2016.09.073

Precise epigenetic regulation of the sex chromosomes is vital for the male germline. Here, we analyze meiosis in eight mouse models deficient for various DNA damage response (DDR) factors, including Fanconi anemia (FA) proteins. We reveal a network of FA and DDR proteins in which FA core factors FANCA, FANCB, and FANCC are essential for FANCD2 foci formation, whereas BRCA1 (FANCS), MDC1, and RNF8 are required for BRCA2 (FANCD1) and SLX4 (FANCP) accumulation on the sex chromosomes during meiosis. In addition, FA proteins modulate distinct histone marks on the sex chromosomes: FA core proteins and FANCD2 regulate H3K9 methylation, while FANCD2 and RNF8 function together to regulate H3K4 methylation independently of FA core proteins. Our data suggest that RNF8 integrates the FA-BRCA pathway. Taken together, our study reveals distinct functions for FA proteins and illuminates the male sex chromosomes as a model to dissect the function of the FA-BRCA pathway.

• 出版日期2016-10-18