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Nonhistone human chromatin protein PC4 is critical for genomic integrity and negatively regulates autophagy
Author(s) -
Sikder Sweta,
Kumari Sujata,
Mustafi Pallabi,
Ramdas Nisha,
Padhi Swatishree,
Saha Arka,
Bhaduri Utsa,
Banerjee Birendranath,
Manjithaya Ravi,
Kundu Tapas K.
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14952
Subject(s) - chromatin , autophagy , microbiology and biotechnology , gene knockdown , biology , histone , gene silencing , epigenetics , gene , genetics , apoptosis
Multifunctional human transcriptional positive co‐activator 4 (PC4) is a bona fide nonhistone component of the chromatin and plays a pivotal role in the process of chromatin compaction and functional genome organization. Knockdown of PC4 expression causes a drastic decompaction which leads to open conformation of the chromatin, and thereby altered nuclear architecture, defects in chromosome segregation and changed epigenetic landscape. Interestingly, these defects do not induce cellular death but result in enhanced cellular proliferation, possibly through enhanced autophagic activity. Moreover, PC4 depletion confers significant resistance to gamma irradiation. Exposure to gamma irradiation further induced autophagy in these cells. Inhibition of autophagy by small molecule inhibitors as well as by silencing of a critical autophagy gene drastically reduces the ability of PC4 knockdown cells to survive. On the contrary, complementation with wild‐type PC4 could reverse this phenomenon, confirming the process of autophagy as the key mechanism for radiation resistance in the absence of PC4. These data connect the unexplored role of chromatin architecture in regulating autophagy during stress conditions such as radiation.